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Adam I, Motyka B, Pearcey J, Tao K, Cowan PJ, West LJ. ABO-A antibody induction in mice is T cell-dependent, estrogen-independent, and modulated by CD22. Am J Transplant 2025; 25:1180-1192. [PMID: 40057198 DOI: 10.1016/j.ajt.2025.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 02/07/2025] [Accepted: 03/01/2025] [Indexed: 03/27/2025]
Abstract
ABO antibodies pose barriers in transplantation but remain poorly studied. We investigated anti-A natural antibodies (nAbs) and induced antibodies (iAbs) in wild-type (WT), CD19KO, and CD22KO mice in the context of major histocompatibility complex-syngeneic or major histocompatibility complex-allogeneic stimulation by ABO-A blood cell membranes (BCM) from A-transgenic mice, or xenogeneic human (Hu-A) BCM. CD19KO mice failed to produce anti-A nAbs and iAbs. Syngeneic A-transgenic-BCM failed to stimulate anti-A iAbs in WT mice, in contrast to allogeneic A-transgenic-BCM and xenogeneic Hu-A-BCM. Hu-A-BCM failed to stimulate anti-A iAbs in CD4-T cell-depleted or CD4KO mice, reversed with CD4-T cell reconstitution. Although anti-A nAbs were absent in estrogen-receptor-α-deficient mice, anti-A iAbs were easily stimulated. Anti-A nAbs were higher in CD22KO than in WT mice, with pubertal females producing higher levels than males. Anti-A iAbs were stimulated in CD22KO mice by syngeneic A-transgenic-BCM or by Hu-A-BCM after CD4T cell depletion. We conclude that anti-A nAbs and iAbs are produced by B1a-cells. In WT mice, stimulation of anti-A iAbs requires exposure to nonself A-antigen together with foreign proteins and is T cell dependent. Without CD22-mediated inhibition, anti-A iAb stimulation does not require foreign protein and is T cell-independent. Anti-A iAbs are estrogen-independent, whereas anti-A nAbs are estrogen-dependent and could be elicited by estrogen in males.
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Affiliation(s)
- Ibrahim Adam
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute and Canadian Donation and Transplantation Research Program, Edmonton, Canada
| | - Bruce Motyka
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute and Canadian Donation and Transplantation Research Program, Edmonton, Canada
| | - Jean Pearcey
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute and Canadian Donation and Transplantation Research Program, Edmonton, Canada
| | - Kesheng Tao
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute and Canadian Donation and Transplantation Research Program, Edmonton, Canada
| | - Peter J Cowan
- Immunology Research Centre, St. Vincent's Hospital Melbourne, Department of Medicine, University of Melbourne, Melbourne, Australia
| | - Lori J West
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute and Canadian Donation and Transplantation Research Program, Edmonton, Canada; Department of Surgery, and Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada.
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2
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Gol Mohammad Pour Afrakoti L, Daneshpour Moghadam S, Hadinezhad P. Alzheimer's disease and the immune system: A comprehensive overview with a focus on B cells, humoral immunity, and immunotherapy. J Alzheimers Dis Rep 2025; 9:25424823251329188. [PMID: 40297057 PMCID: PMC12035277 DOI: 10.1177/25424823251329188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 02/11/2025] [Indexed: 04/30/2025] Open
Abstract
Alzheimer's disease (AD) is a complex neurodegenerative disorder and the major cause of dementia. Amyloid-β (Aβ) and tau aggregation, mitochondrial dysfunction, and microglial dysregulation are key contributors to AD pathogenesis. Impairments in the blood-brain barrier have unveiled the contribution of the immune system, particularly B cells, in AD pathology. B cells, a crucial component of adaptive immunity, exhibit diverse functions, including antigen presentation and antibody production. While their role in neuroinflammatory disorders has been well-documented, their specific function in AD lacks adequate data. This review examines the dual role of the B cells and humoral immunity in modulating brain inflammation in AD and explores recent advancements in passive and active immunotherapeutic strategies targeting AD pathobiology. We summarize preclinical and clinical studies investigating B cell frequency, altered antibody levels, and their implications in neuroinflammation and immunotherapy. Notably, B cells demonstrate protective and pathological roles in AD, influencing neurodegeneration through antibody-mediated clearance of toxic aggregates and inflammatory activation inflammation. Passive immunotherapies targeting Aβ have shown potential in reducing amyloid plaques, while active immunotherapies are emerging as promising strategies, requiring further validation. Understanding the interplay between B cells, humoral immunity, microglia, and mitochondrial dysfunction is critical to unraveling AD pathogenesis. Their dual nature in disease progression underscores the need for precise therapeutic interventions to optimize immunotherapy outcomes and mitigate neuroinflammation effectively.
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Affiliation(s)
| | - Sanam Daneshpour Moghadam
- Department of Diagnostic and Public Health, School of Biotechnology, University of Verona, Verona, Italy
| | - Pezhman Hadinezhad
- Cognitive Neurology, Dementia and Neuropsychiatry Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Adegoke AO, Thangavelu G, Chou TF, Petersen MI, Kakugawa K, May JF, Joannou K, Wang Q, Ellestad KK, Boon L, Bretscher PA, Cheroutre H, Kronenberg M, Baldwin TA, Anderson CC. Internal regulation between constitutively expressed T cell co-inhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants. Open Biol 2024; 14:240178. [PMID: 39471840 PMCID: PMC11521602 DOI: 10.1098/rsob.240178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/23/2024] [Accepted: 09/24/2024] [Indexed: 11/01/2024] Open
Abstract
Immunologic self-tolerance involves signals from co-inhibitory receptors. Several T cell co-inhibitors, including PD-1, are expressed upon activation, whereas CD5 and BTLA are expressed constitutively. The relationship between constitutively expressed co-inhibitors and when they are needed is unknown. Deletion of Btla demonstrated BTLA regulates CD5 expression. Loss of BTLA signals, but not signalling by its ligand, HVEM, leads to increased CD5 expression. Higher CD5 expression set during thymic selection is associated with increased self-recognition, suggesting that BTLA might be needed early to establish self-tolerance. We found that BTLA and PD-1 were needed post-thymic selection in recent thymic emigrants (RTE). RTE lacking BTLA caused a CD4 T cell and MHC class II dependent multi-organ autoimmune disease. Together, our findings identify a negative regulatory pathway between two constitutively expressed co-inhibitors, calibrating their expression. Expression of constitutive and induced co-inhibitory receptors is needed early to establish tolerance in the periphery for RTE.
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Affiliation(s)
| | - Govindarajan Thangavelu
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
- Alberta Diabetes and Transplant Institutes, University of Alberta, Edmonton, AB, Canada
| | - Ting-Fang Chou
- La Jolla Institute for Immunology, La Jolla, CA92037, USA
| | - Marcos I. Petersen
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
| | - Kiyokazu Kakugawa
- Laboratory for Immune Crosstalk, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi-ku, Yokohama230-0045, Japan
| | - Julia F. May
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
| | - Kevin Joannou
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
| | - Qingyang Wang
- La Jolla Institute for Immunology, La Jolla, CA92037, USA
| | - Kristofor K. Ellestad
- Alberta Diabetes and Transplant Institutes, University of Alberta, Edmonton, AB, Canada
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
| | | | - Peter A. Bretscher
- Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Hilde Cheroutre
- La Jolla Institute for Immunology, La Jolla, CA92037, USA
- Laboratory for Immune Crosstalk, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi-ku, Yokohama230-0045, Japan
| | - Mitchell Kronenberg
- La Jolla Institute for Immunology, La Jolla, CA92037, USA
- Department of Molecular Biology, University of California San Diego, La Jolla, CA92093, USA
| | - Troy A. Baldwin
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
| | - Colin C. Anderson
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
- Alberta Diabetes and Transplant Institutes, University of Alberta, Edmonton, AB, Canada
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
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Chu Y, He Y, Zhai W, Huang Y, Tao C, Pang Z, Wang Z, Zhang D, Li H, Jia H. CpG adjuvant enhances humoral and cellular immunity against OVA in different degrees in BALB/c, C57BL/6J, and C57BL/6N mice. Int Immunopharmacol 2024; 138:112593. [PMID: 38972210 DOI: 10.1016/j.intimp.2024.112593] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/09/2024]
Abstract
In lab settings, inbred mouse strains like BALB/c, C57BL/6J, and C57BL/6N are commonly used. Research in immunology and infectious diseases indicates that their Th1 and Th2 immune responses differ. However, the specific differences in the immune response to the vaccination still require investigation. In this study, ovalbumin (OVA) was used as an antigen and CpG-enriched recombinant plasmid (pUC18-CpG) as an adjuvant for immunisation. The level of serum-specific antibody IgG was detected by indirect ELISA. At 35dpi, serum cytokine levels were measured using MILLIPLEX®. T lymphocyte clusters from mouse spleen were examined using flow cytometry to investigate the immunological effects of the CPG-OVA vaccine on three different types of mice. The results showed that pUC18-CpG as an adjuvant could successfully enhance the immune response. BALB/c had the highest level of IgG antibody. In the OVA-only group, the CD4+/CD8+ ratio of the three types of mice was generally increased, and the BALB/c group had the highest ratio. After inoculation with CpG-OVA, the CD4+/CD8+ ratio of the three types of mice was lower than that of the OVA-only group, and C57BL/6J was the lowest. Compared with the CpG-OVA group of the three kinds of mice, the levels of Th2 cytokines IL-6 and IL-10 in BALB/c were increased compared with C57BL/6J and C57BL/6N. After OVA, the six cytokines secreted in C57BL/6J were higher than those in the C57BL/6N OVA group. Therefore, C57 is a better model for examining the function of the vaccine in cellular immunity, whereas BALB/c mice are more prone to humoral immunity. In addition to highlighting the CpG plasmid's ability to successfully activate the immune response of Th1 and Th2, as well as the expression of IgG in vivo and promote T cell immune typing, this study provides valuable insights into immunology and the selection of mouse models for infectious diseases, providing a valuable resource for designing more effective vaccines in the future.
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Affiliation(s)
- Yuanyuan Chu
- College of Animal Science and Technology, Beijing University of Agriculture, Beijing 100096, China; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Yuheng He
- College of Animal Science and Technology, Beijing University of Agriculture, Beijing 100096, China
| | - Wenzhu Zhai
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Ying Huang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Chunhao Tao
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Zhongbao Pang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Zhen Wang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Dekun Zhang
- Taihe Biotechnology Co., Ltd., Nanjing 210031, China
| | - Huanrong Li
- College of Animal Science and Technology, Beijing University of Agriculture, Beijing 100096, China.
| | - Hong Jia
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
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Mattos MS, Vandendriessche S, Waisman A, Marques PE. The immunology of B-1 cells: from development to aging. Immun Ageing 2024; 21:54. [PMID: 39095816 PMCID: PMC11295433 DOI: 10.1186/s12979-024-00455-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 07/17/2024] [Indexed: 08/04/2024]
Abstract
B-1 cells have intricate biology, with distinct function, phenotype and developmental origin from conventional B cells. They generate a B cell receptor with conserved germline characteristics and biased V(D)J recombination, allowing this innate-like lymphocyte to spontaneously produce self-reactive natural antibodies (NAbs) and become activated by immune stimuli in a T cell-independent manner. NAbs were suggested as "rheostats" for the chronic diseases in advanced age. In fact, age-dependent loss of function of NAbs has been associated with clinically-relevant diseases in the elderly, such as atherosclerosis and neurodegenerative disorders. Here, we analyzed comprehensively the ontogeny, phenotypic characteristics, functional properties and emerging roles of B-1 cells and NAbs in health and disease. Additionally, after navigating through the complexities of B-1 cell biology from development to aging, therapeutic opportunities in the field are discussed.
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Affiliation(s)
- Matheus Silvério Mattos
- Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000, Louvain, Belgium
| | - Sofie Vandendriessche
- Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000, Louvain, Belgium
| | - Ari Waisman
- Institute for Molecular Medicine, University Medical Centre of the Johannes Gutenberg University of Mainz, Mainz, Germany
| | - Pedro Elias Marques
- Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000, Louvain, Belgium.
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6
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Ignacio A, Czyz S, McCoy KD. Early life microbiome influences on development of the mucosal innate immune system. Semin Immunol 2024; 73:101885. [PMID: 38788491 DOI: 10.1016/j.smim.2024.101885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 05/11/2024] [Accepted: 05/16/2024] [Indexed: 05/26/2024]
Abstract
The gut microbiota is well known to possess immunomodulatory capacities, influencing a multitude of cellular signalling pathways to maintain host homeostasis. Although the formation of the immune system initiates before birth in a sterile environment, an emerging body of literature indicates that the neonatal immune system is influenced by a first wave of external stimuli that includes signals from the maternal microbiota. A second wave of stimulus begins after birth and must be tightly regulated during the neonatal period when colonization of the host occurs concomitantly with the maturation of the immune system, requiring a fine adjustment between establishing tolerance towards the commensal microbiota and preserving inflammatory responses against pathogenic invaders. Besides integrating cues from commensal microbes, the neonatal immune system must also regulate responses triggered by other environmental signals, such as dietary antigens, which become more complex with the introduction of solid food during the weaning period. This "window of opportunity" in early life is thought to be crucial for the proper development of the immune system, setting the tone of subsequent immune responses in adulthood and modulating the risk of developing chronic and metabolic inflammatory diseases. Here we review the importance of host-microbiota interactions for the development and maturation of the immune system, particularly in the early-life period, highlighting the known mechanisms involved in such communication. This discussion is focused on recent data demonstrating microbiota-mediated education of innate immune cells and its role in the development of lymphoid tissues.
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Affiliation(s)
- Aline Ignacio
- Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Sonia Czyz
- Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Kathy D McCoy
- Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
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7
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Welsh AM, Muljo SA. Post-transcriptional (re)programming of B lymphocyte development: From bench to bedside? Adv Immunol 2024; 161:85-108. [PMID: 38763703 DOI: 10.1016/bs.ai.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/21/2024]
Abstract
Hematopoiesis, a process which generates blood and immune cells, changes significantly during mammalian development. Definitive hematopoiesis is marked by the emergence of long-term hematopoietic stem cells (HSCs). Here, we will focus on the post-transcriptional differences between fetal liver (FL) and adult bone marrow (ABM) HSCs. It remains unclear how or why exactly FL HSCs transition to ABM HSCs, but we aim to leverage their differences to revive an old idea: in utero HSC transplantation. Unexpectedly, the expression of certain RNA-binding proteins (RBPs) play an important role in HSC specification, and can be employed to convert or reprogram adult HSCs back to a fetal-like state. Among other features, FL HSCs have a broad differentiation capacity that includes the ability to regenerate both conventional B and T cells, as well as innate-like or unconventional lymphocytes such as B-1a and marginal zone B (MzB) cells. This chapter will focus on RNA binding proteins, namely LIN28B and IGF2BP3, that are expressed during fetal life and how they promote B-1a cell development. Furthermore, this chapter considers a potential clinical application of synthetic co-expression of LIN28B and IGF2BP3 in HSCs.
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Affiliation(s)
- Alia M Welsh
- Integrative Immunobiology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Stefan A Muljo
- Integrative Immunobiology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States.
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8
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Li Y, Ma Y, Liu Y, Tang N, Zhang W, Huo J, Zhang D. Role of differentiated embryo-chondrocyte expressed gene 2 in immunity. Front Immunol 2024; 15:1335473. [PMID: 38533496 PMCID: PMC10963606 DOI: 10.3389/fimmu.2024.1335473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 02/29/2024] [Indexed: 03/28/2024] Open
Abstract
Differentiated embryo-chondrocyte expressed gene 2 (DEC2) is a member of the basic helix-loop-helix (bHLH) subfamily of transcription factors. DEC2 is implicated in tumor immunotherapy, immune system function regulation, and autoimmune diseases. DEC2 enhances Th2 cell differentiation by regulating the IL-2 and IL-4 signaling pathways and mediates the growth of B-1a cells, thereby promoting the occurrence and development of inflammatory responses. In this study, we review the reported roles of DEC2, including the regulation of immune cell differentiation and cytokine production in various cells in humans, and discuss its potential in treating autoimmune diseases and tumors.
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Affiliation(s)
- Yujing Li
- Department of Pathology, The First Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China
| | - Yinan Ma
- Department of Pathology, The First Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China
| | - Yang Liu
- Department of Pathology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Na Tang
- Department of Pathology, The First Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China
| | - Wenzhu Zhang
- Department of Pathology, The First Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China
| | - Jingru Huo
- Department of Pathology, The First Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China
| | - Di Zhang
- Department of Pathology, The First Hospital of China Medical University, Shenyang, Liaoning, China
- Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China
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Maslanka J, Torres G, Londregan J, Goldman N, Silberman D, Somerville J, Riggs JE. Loss of B1 and marginal zone B cells during ovarian cancer. Cell Immunol 2024; 395-396:104788. [PMID: 38000306 PMCID: PMC10842900 DOI: 10.1016/j.cellimm.2023.104788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/31/2023] [Accepted: 11/20/2023] [Indexed: 11/26/2023]
Abstract
Recent advances in immunotherapy have not addressed the challenge presented by ovarian cancer. Although the peritoneum is an "accessible" locus for this disease there has been limited characterization of the immunobiology therein. We investigated the ID8-C57BL/6J ovarian cancer model and found marked depletion of B1 cells from the ascites of the peritoneal cavity. There was also selective loss of the B1 and marginal zone B cell subsets from the spleen. Immunity to antigens that activate these subsets validated their loss rather than relocation. A marked influx of myeloid-derived suppressor cells correlated with B cell subset depletion. These observations are discussed in the context of the housekeeping burden placed on innate B cells during ovarian cancer and to foster consideration of B cell biology in therapeutic strategies to address this challenge.
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Affiliation(s)
- Jeffrey Maslanka
- Department of Biology, Rider University, Lawrenceville, NJ 08648, USA
| | - Gretel Torres
- Department of Biology, Rider University, Lawrenceville, NJ 08648, USA
| | | | - Naomi Goldman
- Department of Biology, Rider University, Lawrenceville, NJ 08648, USA
| | - Daniel Silberman
- Department of Biology, Rider University, Lawrenceville, NJ 08648, USA
| | - John Somerville
- Department of Biology, Rider University, Lawrenceville, NJ 08648, USA
| | - James E Riggs
- Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
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Suchanek O, Clatworthy MR. Homeostatic role of B-1 cells in tissue immunity. Front Immunol 2023; 14:1106294. [PMID: 37744333 PMCID: PMC10515722 DOI: 10.3389/fimmu.2023.1106294] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 02/27/2023] [Indexed: 09/26/2023] Open
Abstract
To date, studies of tissue-resident immunity have mainly focused on innate immune cells and T cells, with limited data on B cells. B-1 B cells are a unique subset of B cells with innate-like properties, enriched in murine pleural and peritoneal cavities and distinct from conventional B-2 cells in their ontogeny, phenotype and function. Here we discuss how B-1 cells represent exemplar tissue-resident immune cells, summarizing the evidence for their long-term persistence & self-renewal within tissues, differential transcriptional programming shaped by organ-specific environmental cues, as well as their tissue-homeostatic functions. Finally, we review the emerging data supporting the presence and homeostatic role of B-1 cells across non-lymphoid organs (NLOs) both in mouse and human.
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Affiliation(s)
- Ondrej Suchanek
- Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
- NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Menna R. Clatworthy
- Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
- NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
- Wellcome Sanger Institute, Hinxton, United Kingdom
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11
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Chang J, Yamashita M, Padhi AK, Zhang KYJ, Taniuchi I. Impaired tissue homing by the Ikzf3 N159S variant is mediated by interfering with Ikaros function. Front Immunol 2023; 14:1239779. [PMID: 37662955 PMCID: PMC10469740 DOI: 10.3389/fimmu.2023.1239779] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
AIOLOS, encoded by IKZF3, is a member of the IKZF family of proteins that plays an important role in regulating late B-cell differentiation. Human individuals heterozygous for the AIOLOS p.N160S variant displayed impaired humoral immune responses as well as impaired B and T cell development. We have previously reported that a mouse strain harboring an Ikzf3N159S allele that corresponds to human IKZF3N160S recapitulated immune-deficient phenotypes, such as impaired B cell development and loss of CD23 expression. In this study, we investigated the effect of the Ikzf3N159S variant and found that B1a cell development was impaired in Ikzf3N159S/N159S mice. In addition, CD62L expression was severely decreased in both B and T lymphocytes by the Ikzf3N159S mutation, in a dose-dependent manner. Mixed bone marrow chimera experiments have revealed that most immunodeficient phenotypes, including low CD62L expression, occur in intrinsic cells. Interestingly, while Ikzf3N159S/N159S lymphocytes were still present in the spleen, they were completely outcompeted by control cells in the lymph nodes, suggesting that the capacity for homing or retention in the lymph nodes was lost due to the Ikzf3N159S mutation. The homing assay confirmed severely decreased homing abilities to lymph nodes of Ikzf3N159S/N159S B and T lymphocytes but selective enrichment of CD62L expressing Ikzf3N159S/N159S lymphocytes in lymph nodes. This finding suggests that impaired CD62L expression is the major reason for the impaired homing capacity caused by the Ikzf3N159S mutation. Interestingly, an excess amount of Ikaros, but not Aiolos, restored CD62L expression in Ikzf3N159S/N159S B cells. Together with the loss of CD62L expression due to Ikaros deficiency, the AiolosN159S mutant protein likely interferes with Ikaros function through heterodimerization, at least in activating the Sell gene encoding CD62L expression. Thus, our results revealed that AiolosN159S causes some immunodeficient phenotypes via the pathogenesis referred to as the heterodimeric interference as observed for AiolosG158R variant.
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Affiliation(s)
- Jingjie Chang
- Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
| | - Motoi Yamashita
- Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
- Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Aditya K. Padhi
- Laboratory for Structural Bioinformatics, RIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan
| | - Kam Y. J. Zhang
- Laboratory for Structural Bioinformatics, RIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan
| | - Ichiro Taniuchi
- Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
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12
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Joyce S, Okoye GD, Driver JP. Die Kämpfe únd schláchten-the struggles and battles of innate-like effector T lymphocytes with microbes. Front Immunol 2023; 14:1117825. [PMID: 37168859 PMCID: PMC10165076 DOI: 10.3389/fimmu.2023.1117825] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 03/22/2023] [Indexed: 05/13/2023] Open
Abstract
The large majority of lymphocytes belong to the adaptive immune system, which are made up of B2 B cells and the αβ T cells; these are the effectors in an adaptive immune response. A multitudinous group of lymphoid lineage cells does not fit the conventional lymphocyte paradigm; it is the unconventional lymphocytes. Unconventional lymphocytes-here called innate/innate-like lymphocytes, include those that express rearranged antigen receptor genes and those that do not. Even though the innate/innate-like lymphocytes express rearranged, adaptive antigen-specific receptors, they behave like innate immune cells, which allows them to integrate sensory signals from the innate immune system and relay that umwelt to downstream innate and adaptive effector responses. Here, we review natural killer T cells and mucosal-associated invariant T cells-two prototypic innate-like T lymphocytes, which sense their local environment and relay that umwelt to downstream innate and adaptive effector cells to actuate an appropriate host response that confers immunity to infectious agents.
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Affiliation(s)
- Sebastian Joyce
- Department of Veterans Affairs, Tennessee Valley Healthcare Service, Nashville, TN, United States
- Department of Pathology, Microbiology and Immunology, The Vanderbilt Institute for Infection, Immunology and Inflammation and Vanderbilt Center for Immunology, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Gosife Donald Okoye
- Department of Pathology, Microbiology and Immunology, The Vanderbilt Institute for Infection, Immunology and Inflammation and Vanderbilt Center for Immunology, Vanderbilt University Medical Center, Nashville, TN, United States
| | - John P. Driver
- Division of Animal Sciences, University of Missouri, Columbia, MO, United States
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13
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Sakai J, Yang J, Chou CK, Wu WW, Akkoyunlu M. B cell receptor-induced IL-10 production from neonatal mouse CD19 +CD43 - cells depends on STAT5-mediated IL-6 secretion. eLife 2023; 12:83561. [PMID: 36735294 PMCID: PMC9934864 DOI: 10.7554/elife.83561] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 01/31/2023] [Indexed: 02/04/2023] Open
Abstract
Newborns are unable to reach the adult-level humoral immune response partly due to the potent immunoregulatory role of IL-10. Increased IL-10 production by neonatal B cells has been attributed to the larger population of IL-10-producting CD43+ B-1 cells in neonates. Here, we show that neonatal mouse CD43- non-B-1 cells also produce substantial amounts of IL-10 following B cell antigen receptor (BCR) activation. In neonatal mouse CD43- non-B-1 cells, BCR engagement activated STAT5 under the control of phosphorylated forms of signaling molecules Syk, Btk, PKC, FAK, and Rac1. Neonatal STAT5 activation led to IL-6 production, which in turn was responsible for IL-10 production in an autocrine/paracrine fashion through the activation of STAT3. In addition to the increased IL-6 production in response to BCR stimulation, elevated expression of IL-6Rα expression in neonatal B cells rendered them highly susceptible to IL-6-mediated STAT3 phosphorylation and IL-10 production. Finally, IL-10 secreted from neonatal mouse CD43- non-B-1 cells was sufficient to inhibit TNF-α secretion by macrophages. Our results unveil a distinct mechanism of IL-6-dependent IL-10 production in BCR-stimulated neonatal CD19+CD43- B cells.
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Affiliation(s)
- Jiro Sakai
- Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, The US Food and Drug AdministrationSilver SpringUnited States
| | - Jiyeon Yang
- Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, The US Food and Drug AdministrationSilver SpringUnited States
| | - Chao-Kai Chou
- Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, United States Food and Drug AdministrationSilver SpringUnited States
| | - Wells W Wu
- Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, United States Food and Drug AdministrationSilver SpringUnited States
| | - Mustafa Akkoyunlu
- Laboratory of Bacterial Polysaccharides, Division of Bacterial Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, The US Food and Drug AdministrationSilver SpringUnited States
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14
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Hu YZ, Li Q, Wang PF, Li XP, Hu ZL. Multiple functions and regulatory network of miR-150 in B lymphocyte-related diseases. Front Oncol 2023; 13:1140813. [PMID: 37182123 PMCID: PMC10172652 DOI: 10.3389/fonc.2023.1140813] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 04/06/2023] [Indexed: 05/16/2023] Open
Abstract
MicroRNAs (miRNAs) play vital roles in the post-transcriptional regulation of gene expression. Previous studies have shown that miR-150 is a crucial regulator of B cell proliferation, differentiation, metabolism, and apoptosis. miR-150 regulates the immune homeostasis during the development of obesity and is aberrantly expressed in multiple B-cell-related malignant tumors. Additionally, the altered expression of MIR-150 is a diagnostic biomarker of various autoimmune diseases. Furthermore, exosome-derived miR-150 is considered as prognostic tool in B cell lymphoma, autoimmune diseases and immune-mediated disorders, suggesting miR-150 plays a vital role in disease onset and progression. In this review, we summarized the miR-150-dependent regulation of B cell function in B cell-related immune diseases.
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Affiliation(s)
- Yue-Zi Hu
- Clinical Laboratory, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Qiao Li
- Department of Anesthesiology, The Second Affiliated Xiangya Hospital, Central South University, Changsha, China
| | - Peng-Fei Wang
- Department of Anesthesiology, The Second Affiliated Xiangya Hospital, Central South University, Changsha, China
| | - Xue-Ping Li
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, United States
| | - Zhao-Lan Hu
- Department of Anesthesiology, The Second Affiliated Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Zhao-Lan Hu,
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15
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Sayin I, Chong AS. Beyond Adaptive Alloreactivity: Contribution of Innate B Cells to Allograft Inflammation and Rejection. Transplantation 2023; 107:98-104. [PMID: 36404414 PMCID: PMC9772142 DOI: 10.1097/tp.0000000000004377] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Innate B cells are a heterogeneous group of cells that function in maintaining homeostatic levels of circulating natural antibodies and being the first line of defense against infections. Innate B-1 cells and marginal zone B cells may relocate to lymphoid follicles and differentiate into cytokine and antibody-secreting cells in T-independent and T-dependent manners. Although marginal zone B cells are widely described in humans, the presence of B-1 cells is more controversial. Here, we review the basic features of the innate B-cell subsets identified in mice and their equivalent in humans, as well as their potential roles in transplantation. We summarize the findings of Cascalho and colleagues on the unexpected protective role of tumor necrosis factor receptor superfamily member 13B in regulating circulating levels of protective natural immunoglobulin M, and the studies by Zorn and colleagues on the potential pathogenic role for polyreactive innate B cells infiltrating allograft explants. Finally, we discuss our studies that took a transcriptomic approach to identify innate B cells infiltrating kidney allografts with antibody-mediated rejection and to demonstrate that local antigens within the allograft together with inflammation may induce a loss of B-cell tolerance.
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Affiliation(s)
- Ismail Sayin
- Department of Surgery, The University of Chicago, Chicago, Illinois, United States
| | - Anita S. Chong
- Department of Surgery, The University of Chicago, Chicago, Illinois, United States
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16
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Daum P, Ottmann SR, Meinzinger J, Schulz SR, Côrte-Real J, Hauke M, Roth E, Schuh W, Mielenz D, Jäck HM, Pracht K. The microRNA processing subunit DGCR8 is required for a T cell-dependent germinal center response. Front Immunol 2022; 13:991347. [PMID: 36591274 PMCID: PMC9800915 DOI: 10.3389/fimmu.2022.991347] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 11/28/2022] [Indexed: 12/23/2022] Open
Abstract
We have previously shown that the microRNA (miRNA) processor complex consisting of the RNAse Drosha and the DiGeorge Critical Region (DGCR) 8 protein is essential for B cell maturation. To determine whether miRNA processing is required to initiate T cell-mediated antibody responses, we deleted DGCR8 in maturing B2 cells by crossing a mouse with loxP-flanked DGCR8 alleles with a CD23-Cre mouse. As expected, non-immunized mice showed reduced numbers of mature B2 cells and IgG-secreting cells and diminished serum IgG titers. In accordance, germinal centers and antigen-specific IgG-secreting cells were absent in mice immunized with T-dependent antigens. Therefore, DGCR8 is required to mount an efficient T-dependent antibody response. However, DGCR8 deletion in B1 cells was incomplete, resulting in unaltered B1 cell numbers and normal IgM and IgA titers in DGCR8-knock-out mice. Therefore, this mouse model could be used to analyze B1 responses in the absence of functional B2 cells.
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17
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Zhai S, Cao M, Zhou H, Zhu H, Xu T, Wang Y, Wang X, Cai Z. H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formation. Front Immunol 2022; 13:959021. [PMID: 36532012 PMCID: PMC9750791 DOI: 10.3389/fimmu.2022.959021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 11/14/2022] [Indexed: 12/03/2022] Open
Abstract
B cells, which consist of two well-defined populations: B1 and B2 cells, which can produce antibodies that are essential for host protection against infections, through virus neutralization, opsonization and antibody-dependent cellular cytotoxicity. Epigenetic modifications, such as DNA methylation and histone modification could regulate immune cell differentiation and functions. In this study, we found a significant reduction of GC response in the B cell specific knockout of H3K36 methyltransferase NSD1 (Mb1-Cre+ NSD1fl/fl, NSD1B KO) mice compared with the wildtype control (Mb1-Cre+ NSD1+/+, NSD1B WT). We also demonstrated reduced production of high-affinity antibody, but increased production of low-affinity antibody in the NSD1B KO mice. Further analysis revealed that loss of NSD1 promoted the development of B1 cells by increasing the expression of Rap1b and Arid3a. In conclusion, our data suggest that NSD1 plays an important role in regulation the development of B1 and B2 cells, and the process of germinal center formation and high-affinity antibody production.
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Affiliation(s)
- Sulan Zhai
- Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, China
| | - Min Cao
- Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, China
| | - Han Zhou
- Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, China,Reproductive Medicine Centre, Changzhou No. 2 People’s Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, China
| | - Huamin Zhu
- Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, China
| | - Tongchang Xu
- Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, China
| | - Yuliang Wang
- Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, China
| | - Xiaoming Wang
- Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, China,State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China,National Health Commission (NHC) Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China,*Correspondence: Xiaoming Wang, ; Zhenming Cai,
| | - Zhenming Cai
- Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, China,*Correspondence: Xiaoming Wang, ; Zhenming Cai,
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18
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Fortmann MI, Dirks J, Goedicke-Fritz S, Liese J, Zemlin M, Morbach H, Härtel C. Immunization of preterm infants: current evidence and future strategies to individualized approaches. Semin Immunopathol 2022; 44:767-784. [PMID: 35922638 PMCID: PMC9362650 DOI: 10.1007/s00281-022-00957-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 07/08/2022] [Indexed: 12/15/2022]
Abstract
Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants benefit greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efficacy due to preterm infants' distinct immunological features. A significant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specificities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specific recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained inflammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future.
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Affiliation(s)
- Mats Ingmar Fortmann
- Department of Pediatrics, University Lübeck, University Hospital Schleswig-Holstein Campus Lübeck, Lübeck, Germany
| | - Johannes Dirks
- Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany
| | - Sybelle Goedicke-Fritz
- Department of General Pediatrics and Neonatology, Faculty of Medicine, Saarland University Hospital and Saarland University, Homburg, Germany
| | - Johannes Liese
- Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany
| | - Michael Zemlin
- Department of General Pediatrics and Neonatology, Faculty of Medicine, Saarland University Hospital and Saarland University, Homburg, Germany
| | - Henner Morbach
- Department of General Pediatrics and Neonatology, Faculty of Medicine, Saarland University Hospital and Saarland University, Homburg, Germany
| | - Christoph Härtel
- Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany.
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19
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Baumgarth N. Breaking the Paradigm: Selection of Self-Reactive Natural Antibodies. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2022; 209:1621-1623. [PMID: 36253068 PMCID: PMC9586457 DOI: 10.4049/jimmunol.2200406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Abstract
This Pillars of Immunology article is a commentary on “Positive Selection of Natural Autoreactive B Cells,” a pivotal article written by K. Hayakawa, M. Asano, S. A. Shinton, M. Gui, D. Allman, C. L. Stewart, J. Silver, and R. R. Hardy, and published in Science, in 1999. https://doi.org/10.1126/science.285.5424.113.
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Affiliation(s)
- Nicole Baumgarth
- Center for Immunology and Infectious Diseases, University of California Davis, Davis, CA
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20
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Lunderberg JM, Dutta S, Collier ARY, Lee JS, Hsu YM, Wang Q, Zheng W, Hao S, Zhang H, Feng L, Robson SC, Gao W, Riedel S. Pan-neutralizing, germline-encoded antibodies against SARS-CoV-2: Addressing the long-term problem of escape variants. Front Immunol 2022; 13:1032574. [DOI: 10.3389/fimmu.2022.1032574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 10/14/2022] [Indexed: 11/13/2022] Open
Abstract
Despite the initially reported high efficacy of vaccines directed against ancestral SARS-CoV-2, repeated infections in both unvaccinated and vaccinated populations remain a major global health challenge. Because of mutation-mediated immune escape by variants-of-concern (VOC), approved neutralizing antibodies (neutAbs) effective against the original strains have been rendered non-protective. Identification and characterization of mutation-independent pan-neutralizing antibody responses are therefore essential for controlling the pandemic. Here, we characterize and discuss the origins of SARS-CoV-2 neutAbs, arising from either natural infection or following vaccination. In our study, neutAbs in COVID-19 patients were detected using the combination of two lateral flow immunoassay (LFIA) tests, corroborated by plaque reduction neutralization testing (PRNT). A point-of-care neutAb LFIA, NeutraXpress™, was validated using serum samples from historical pre-COVID-19 negative controls, patients infected with other respiratory pathogens, and PCR-confirmed COVID-19 patients. Surprisingly, potent neutAb activity was mainly noted in patients generating both IgM and IgG against the Spike receptor-binding domain (RBD), in contrast to samples possessing anti-RBD IgG alone. We propose that low-affinity, high-avidity, germline-encoded natural IgM and subsequent generation of class-switched IgG may have an underappreciated role in cross-protection, potentially offsetting immune escape by SARS-CoV-2 variants. We suggest Reverse Vaccinology 3.0 to further exploit this innate-like defense mechanism. Our proposition has potential implications for immunogen design, and provides strategies to elicit pan-neutAbs from natural B1-like cells. Refinements in future immunization protocols might further boost long-term cross-protection, even at the mucosal level, against clinical manifestations of COVID-19.
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21
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Souza OF, Popi AF. Role of microRNAs in B-Cell Compartment: Development, Proliferation and Hematological Diseases. Biomedicines 2022; 10:biomedicines10082004. [PMID: 36009551 PMCID: PMC9405569 DOI: 10.3390/biomedicines10082004] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 07/29/2022] [Accepted: 08/14/2022] [Indexed: 11/24/2022] Open
Abstract
B-cell development is a very orchestrated pathway that involves several molecules, such as transcription factors, cytokines, microRNAs, and also different cells. All these components maintain the ideal microenvironment and control B-cell differentiation. MicroRNAs are small non-coding RNAs that bind to target mRNA to control gene expression. These molecules could circulate in the body in a free form, protein-bounded, or encapsulated into extracellular vesicles, such as exosomes. The comprehension of the role of microRNAs in the B-cell development was possible based on microRNA profile of each B-cell stage and functional studies. Herein, we report the knowledge about microRNAs in the B-cell the differentiation, proliferation, and also in hematological malignancies.
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22
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Fernandez NC, Shinoda K. The Role of B Lymphocyte Subsets in Adipose Tissue Development, Metabolism, and Aging. Compr Physiol 2022; 12:4133-4145. [PMID: 35950657 DOI: 10.1002/cphy.c220006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Adipose tissue contains resident B lymphocytes (B cells) with varying immune functions and mechanisms, depending on the adipose depot type and location. The heterogeneity of B cells and their functions affect the immunometabolism of the adipose tissue in aging and age-associated metabolic disorders. B cells exist in categorizations of subsets that have developmental or phenotypic differences with varying functionalities. Subsets can be categorized as either protective or pathogenic depending on their secretion profile or involvement in metabolic maintenance. In this article, we summarized recent finding on the B cell heterogeneity and discuss how we can utilize our current knowledge of adipose resident B lymphocytes for potential treatment for age-associated metabolic disorders. © 2022 American Physiological Society. Compr Physiol 12: 1-13, 2022.
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Affiliation(s)
- Nicole C Fernandez
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Kosaku Shinoda
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA
- Department of Medicine, Division of Endocrinology & Diabetes, Albert Einstein College of Medicine, Bronx, New York, USA
- Fleischer Institute for Diabetes and Metabolism, Bronx, New York, USA
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23
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Suo C, Dann E, Goh I, Jardine L, Kleshchevnikov V, Park JE, Botting RA, Stephenson E, Engelbert J, Tuong ZK, Polanski K, Yayon N, Xu C, Suchanek O, Elmentaite R, Domínguez Conde C, He P, Pritchard S, Miah M, Moldovan C, Steemers AS, Mazin P, Prete M, Horsfall D, Marioni JC, Clatworthy MR, Haniffa M, Teichmann SA. Mapping the developing human immune system across organs. Science 2022; 376:eabo0510. [PMID: 35549310 PMCID: PMC7612819 DOI: 10.1126/science.abo0510] [Citation(s) in RCA: 170] [Impact Index Per Article: 56.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Single-cell genomics studies have decoded the immune-cell composition of several human prenatal organs but were limited in understanding the developing immune system as a distributed network across tissues. We profiled nine prenatal tissues combining single-cell RNA sequencing, antigen-receptor sequencing, and spatial transcriptomics to reconstruct the developing human immune system. This revealed the late acquisition of immune effector functions by myeloid and lymphoid cell subsets and the maturation of monocytes and T cells prior to peripheral tissue seeding. Moreover, we uncovered system-wide blood and immune cell development beyond primary hematopoietic organs, characterized human prenatal B1 cells, and shed light on the origin of unconventional T cells. Our atlas provides both valuable data resources and biological insights that will facilitate cell engineering, regenerative medicine, and disease understanding.
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Affiliation(s)
- Chenqu Suo
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.,Department of Paediatrics, Cambridge University Hospitals, Hills Road, Cambridge, UK
| | - Emma Dann
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
| | - Issac Goh
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Laura Jardine
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.,Haematology Department, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | | | - Jong-Eun Park
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.,Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea
| | - Rachel A Botting
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Emily Stephenson
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Justin Engelbert
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Zewen Kelvin Tuong
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.,Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Krzysztof Polanski
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
| | - Nadav Yayon
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.,European Molecular Biology Laboratory European Bioinformatics Institute, Hinxton, Cambridge, UK
| | - Chuan Xu
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
| | - Ondrej Suchanek
- Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Rasa Elmentaite
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
| | | | - Peng He
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.,European Molecular Biology Laboratory European Bioinformatics Institute, Hinxton, Cambridge, UK
| | - Sophie Pritchard
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
| | - Mohi Miah
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Corina Moldovan
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | | | - Pavel Mazin
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
| | - Martin Prete
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
| | - Dave Horsfall
- Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - John C Marioni
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.,European Molecular Biology Laboratory European Bioinformatics Institute, Hinxton, Cambridge, UK.,Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK
| | - Menna R Clatworthy
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.,Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK
| | - Muzlifah Haniffa
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.,Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.,Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Sarah A Teichmann
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.,Theory of Condensed Matter, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK
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24
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Webster SE, Ryali B, Clemente MJ, Tsuji NL, Holodick NE. Sex Influences Age-Related Changes in Natural Antibodies and CD5 + B-1 Cells. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2022; 208:1755-1771. [PMID: 35256511 PMCID: PMC8976758 DOI: 10.4049/jimmunol.2101150] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 01/30/2022] [Indexed: 11/19/2022]
Abstract
Natural Abs are primarily produced by B-1 cells and are essential for protection against Streptococcus pneumoniae The incidence and mortality rate for pneumococcal infection increases dramatically after age 65, disproportionately affecting males in both human and murine systems. To date, there is a significant gap in our understanding of the relationship among sex, aging, natural IgM efficacy, and the natural IgM repertoire. Our investigation demonstrates that the protective capacity of serum IgM against pneumococcal infection is maintained in IgM obtained from aged female mice but absent in IgM from aged male mice. To understand this difference in protective capacity, we examined serum Ig, discovering that the protective change was not associated with shifts in levels of phosphorylcholine (PC)- or pneumococcal capsular polysaccharide serotype 3-specific IgM. Interestingly, we observed that aged females have an increase in the total number of CD5+ B-1 cells, higher serum IL-5 levels, and a larger percentage of aged female CD5+ B-1 cells that express CD86 as compared with aged males. Furthermore, single-cell IgM repertoire analysis from peritoneal PC+, splenic PC+, and bone marrow CD5+ B-1 cell subsets demonstrated greater diversity with age and a higher level of germline status in female mice than previously observed in studies of aged male mice. Aged female CD5+ B-1 cells also expressed higher levels of transcripts associated with cell activity and self-renewal, such as Nanog and Hmga2 Taken together, these data indicate that females maintain a more diverse and active CD5+ B-1 cell pool and natural IgM repertoire, which has implications for sex-related susceptibility to infection and disease.
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Affiliation(s)
- Sarah E Webster
- Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI.,Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI
| | - Brinda Ryali
- Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI.,Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI.,Department of Medicine, Rush University Medical Center, Chicago, IL; and
| | - Michael J Clemente
- Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI.,Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI.,Flow Cytometry and Imaging Core, Western Michigan Homer Stryker M.D. School of Medicine, Kalamazoo, MI
| | - Naomi L Tsuji
- Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI.,Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI
| | - Nichol E Holodick
- Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI; .,Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI
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25
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Halperin ST, ’t Hart BA, Luchicchi A, Schenk GJ. The Forgotten Brother: The Innate-like B1 Cell in Multiple Sclerosis. Biomedicines 2022; 10:606. [PMID: 35327408 PMCID: PMC8945227 DOI: 10.3390/biomedicines10030606] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/21/2022] [Accepted: 03/01/2022] [Indexed: 02/04/2023] Open
Abstract
Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS), traditionally considered a chronic autoimmune attack against the insulating myelin sheaths around axons. However, the exact etiology has not been identified and is likely multi-factorial. Recently, evidence has been accumulating that implies that autoimmune processes underlying MS may, in fact, be triggered by pathological processes initiated within the CNS. This review focuses on a relatively unexplored immune cell-the "innate-like" B1 lymphocyte. The B1 cell is a primary-natural-antibody- and anti-inflammatory-cytokine-producing cell present in the healthy brain. It has been recently shown that its frequency and function may differ between MS patients and healthy controls, but its exact involvement in the MS pathogenic process remains obscure. In this review, we propose that this enigmatic cell may play a more prominent role in MS pathology than ever imagined. We aim to shed light on the human B1 cell in health and disease, and how dysregulation in its delicate homeostatic role could impact MS. Furthermore, novel therapeutic avenues to restore B1 cells' beneficial functions will be proposed.
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Affiliation(s)
| | | | - Antonio Luchicchi
- Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit, 1081 HZ Amsterdam, The Netherlands; (S.T.H.); (B.A.’t.H.)
| | - Geert J. Schenk
- Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit, 1081 HZ Amsterdam, The Netherlands; (S.T.H.); (B.A.’t.H.)
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26
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Londregan J, Maslanka J, Goldman N, Somerville J, Riggs JE. IgD ligation allows peritoneal cavity B cell proliferation. Immunobiology 2022; 227:152181. [PMID: 35077917 PMCID: PMC8918009 DOI: 10.1016/j.imbio.2022.152181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 12/24/2021] [Accepted: 01/17/2022] [Indexed: 11/19/2022]
Abstract
Atypical cytokine production and immune cell subset ratios, particularly those that include high proportions of macrophages, characterize tumor microenvironments (TMEs). TMEs can be modeled by culturing peritoneal cavity (PerC) cells which have a high macrophage to lymphocyte ratio. With TCR or BCR ligation, PerC lymphocyte proliferation is tempered by macrophages. However, PHA (T cells) and anti-CD40 (B cells) are activators that induce proliferation. Herein, we report that ligating IgD, in contrast to IgM, triggers PerC B cell proliferation. IL-4 addition enhanced the IgD response for BALB/c PerC B cells but suppressed that of C57BL/6 mice. Intriguingly, concurrent ligation of IgD and CD3ε rescued a PerC T cell proliferative response. These results serve to expand the list of targets for promoting cellular and humoral immunity in conditions that model macrophage-rich TMEs.
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Affiliation(s)
| | - Jeffrey Maslanka
- Biology Department, Rider University, Lawrenceville, NJ 08648, USA
| | - Naomi Goldman
- Biology Department, Rider University, Lawrenceville, NJ 08648, USA
| | - John Somerville
- Biology Department, Rider University, Lawrenceville, NJ 08648, USA
| | - James E Riggs
- Biology Department, Rider University, Lawrenceville, NJ 08648, USA.
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27
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Tejon G, Valdivieso N, Flores-Santibañez F, Barra-Valdebenito V, Martínez V, Rosemblatt M, Sauma D, Bono MR. Phenotypic and functional alterations of peritoneal macrophages in lupus-prone mice. Mol Biol Rep 2022; 49:4193-4204. [PMID: 35211864 PMCID: PMC9262788 DOI: 10.1007/s11033-022-07252-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 02/09/2022] [Indexed: 11/28/2022]
Abstract
Background Several studies have demonstrated the contribution of innate immune cells, including macrophages, in promoting systemic lupus erythematosus (SLE). Macrophages, one of the most abundant cell populations in the peritoneal cavity, are considered multifunctional cells with phenotypic plasticity. However, the functional properties of peritoneal macrophages in steady-state and during the progression of SLE remain poorly defined. Methods and results Using the [NZB × NZW]F1 (BWF1) murine model of SLE, we analyzed the phenotype and function of peritoneal macrophages during the disease’s onset. We found a higher frequency of peritoneal macrophages and B1a cells in BWF1-diseased mice than age-matched controls. Additionally, macrophages from diseased animals expressed lower levels of CD206, MHC-II, and Sirpα. RNAseq analysis identified 286 differentially expressed genes in peritoneal macrophages from diseased-BWF1 mice compared to control mice. Functional experiments demonstrate that peritoneal macrophages from diseased-BWF1 mice secrete higher levels of pro-inflammatory cytokines when activated with TLR7 and TLR9 agonists, and they were less efficient in suppressing the activation and proliferation of peritoneal LPS-activated B cells. These data demonstrate that peritoneal macrophages from BWF1-diseased mice present phenotypic and functional alterations shifting to a more pro-inflammatory state. Conclusions The increase of macrophages with an altered phenotype and function together with the accumulation of B1a cells in the peritoneal cavity of diseased-BWF1 mice may promote the progression of the disease. Advancing awareness of the role and phenotype of peritoneal macrophages in SLE may contribute to a better understanding of these types of diseases and the development of novel therapies. Supplementary Information The online version contains supplementary material available at 10.1007/s11033-022-07252-0.
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Affiliation(s)
- Gabriela Tejon
- Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile
- Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile
| | - Nicolás Valdivieso
- Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile
| | | | | | - Víctor Martínez
- FAVET-INBIOGEN, Facultad de Ciencias Veterinarias, Universidad de Chile, Santiago, Chile
| | - Mario Rosemblatt
- Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile
- Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile
- Centro Ciencia & Vida, Santiago, Chile
| | - Daniela Sauma
- Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile
| | - María Rosa Bono
- Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
- Centro Ciencia & Vida, Santiago, Chile.
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28
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Barington L, Christensen LVV, Pedersen KK, Niss Arfelt K, Roumain M, Jensen KHR, Kjær VMS, Daugvilaite V, Kearney JF, Christensen JP, Hjortø GM, Muccioli GG, Holst PJ, Rosenkilde MM. GPR183 Is Dispensable for B1 Cell Accumulation and Function, but Affects B2 Cell Abundance, in the Omentum and Peritoneal Cavity. Cells 2022; 11:cells11030494. [PMID: 35159303 PMCID: PMC8834096 DOI: 10.3390/cells11030494] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/25/2022] [Accepted: 01/27/2022] [Indexed: 02/06/2023] Open
Abstract
B1 cells constitute a specialized subset of B cells, best characterized in mice, which is abundant in body cavities, including the peritoneal cavity. Through natural and antigen-induced antibody production, B1 cells participate in the early defense against bacteria. The G protein-coupled receptor 183 (GPR183), also known as Epstein-Barr virus-induced gene 2 (EBI2), is an oxysterol-activated chemotactic receptor that regulates migration of B cells. We investigated the role of GPR183 in B1 cells in the peritoneal cavity and omentum. B1 cells expressed GPR183 at the mRNA level and migrated towards the GPR183 ligand 7α,25-dihydroxycholesterol (7α,25-OHC). GPR183 knock-out (KO) mice had smaller omenta, but with normal numbers of B1 cells, whereas they had fewer B2 cells in the omentum and peritoneal cavity than wildtype (WT) mice. GPR183 was not responsible for B1 cell accumulation in the omentum in response to i.p. lipopolysaccharide (LPS)-injection, in spite of a massive increase in 7α,25-OHC levels. Lack of GPR183 also did not affect B1a- or B1b cell-specific antibody responses after vaccination. In conclusion, we found that GPR183 is non-essential for the accumulation and function of B1 cells in the omentum and peritoneal cavity, but that it influences the abundance of B2 cells in these compartments.
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Affiliation(s)
- Line Barington
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.B.); (L.v.V.C.); (K.K.P.); (K.N.A.); (K.H.R.J.); (V.M.S.K.); (V.D.); (G.M.H.)
| | - Liv von Voss Christensen
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.B.); (L.v.V.C.); (K.K.P.); (K.N.A.); (K.H.R.J.); (V.M.S.K.); (V.D.); (G.M.H.)
| | - Kristian Kåber Pedersen
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.B.); (L.v.V.C.); (K.K.P.); (K.N.A.); (K.H.R.J.); (V.M.S.K.); (V.D.); (G.M.H.)
| | - Kristine Niss Arfelt
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.B.); (L.v.V.C.); (K.K.P.); (K.N.A.); (K.H.R.J.); (V.M.S.K.); (V.D.); (G.M.H.)
| | - Martin Roumain
- Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium; (M.R.); (G.G.M.)
| | - Kristian Høj Reveles Jensen
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.B.); (L.v.V.C.); (K.K.P.); (K.N.A.); (K.H.R.J.); (V.M.S.K.); (V.D.); (G.M.H.)
| | - Viktoria Madeline Skovgaard Kjær
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.B.); (L.v.V.C.); (K.K.P.); (K.N.A.); (K.H.R.J.); (V.M.S.K.); (V.D.); (G.M.H.)
| | - Viktorija Daugvilaite
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.B.); (L.v.V.C.); (K.K.P.); (K.N.A.); (K.H.R.J.); (V.M.S.K.); (V.D.); (G.M.H.)
| | - John F. Kearney
- Division of Developmental and Clinical Immunology, Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
| | - Jan Pravsgaard Christensen
- Infectious Immunology Group, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark;
| | - Gertrud Malene Hjortø
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.B.); (L.v.V.C.); (K.K.P.); (K.N.A.); (K.H.R.J.); (V.M.S.K.); (V.D.); (G.M.H.)
| | - Giulio G. Muccioli
- Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium; (M.R.); (G.G.M.)
| | - Peter Johannes Holst
- Experimental Vaccinology Group, Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark;
- InProTher ApS, 2200 Copenhagen, Denmark
| | - Mette Marie Rosenkilde
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.B.); (L.v.V.C.); (K.K.P.); (K.N.A.); (K.H.R.J.); (V.M.S.K.); (V.D.); (G.M.H.)
- Correspondence:
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29
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Lim SY, Yamaguchi K, Itakura M, Chikazawa M, Matsuda T, Uchida K. Unique B-1 cells specific for both N-pyrrolated proteins and DNA evolve with apolipoprotein E deficiency. J Biol Chem 2022; 298:101582. [PMID: 35031322 PMCID: PMC8844855 DOI: 10.1016/j.jbc.2022.101582] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/06/2022] [Accepted: 01/10/2022] [Indexed: 11/28/2022] Open
Abstract
Lysine N-pyrrolation, a posttranslational modification, which converts lysine residues to Nε-pyrrole-L-lysine, imparts electronegative properties to proteins, causing them to mimic DNA. Apolipoprotein E (apoE) has been identified as a soluble receptor for pyrrolated proteins (pyrP), and accelerated lysine N-pyrrolation has been observed in apoE-deficient (apoE−/−) hyperlipidemic mice. However, the impact of pyrP accumulation consequent to apoE deficiency on the innate immune response remains unclear. Here, we investigated B-1a cells known to produce germline-encoded immunoglobulin M (IgM) from mice deficient in apoE and identified a particular cell population that specifically produces IgM antibodies against pyrP and DNA. We demonstrated an expansion of B-1a cells involved in IgM production in the peritoneal cavity of apoE−/− mice compared with wild-type mice, consistent with a progressive increase of IgM response in the mouse sera. We found that pyrP exhibited preferential binding to B-1a cells and facilitated the production of IgM. B cell receptor analysis of pyrP-specific B-1a cells showed restricted usage of gene segments selected from the germline gene set; most sequences contained high levels of non-templated-nucleotide additions (N-additions) that could contribute to junctional diversity of B cell receptors. Finally, we report that a subset of monoclonal IgM antibodies against pyrP/DNA established from the apoE−/− mice also contained abundant N-additions. These results suggest that the accumulation of pyrP due to apoE deficiency may influence clonal diversity in the pyrP-specific B cell repertoire. The discovery of these unique B-1a cells for pyrP/DNA provides a key link connecting covalent protein modification, lipoprotein metabolism, and innate immunity.
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Affiliation(s)
- Sei-Young Lim
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
| | - Kosuke Yamaguchi
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
| | - Masanori Itakura
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
| | - Miho Chikazawa
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
| | - Tomonari Matsuda
- Research Center for Environmental Quality Management, Kyoto University, Otsu, Shiga, Japan
| | - Koji Uchida
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan; Japan Agency for Medical Research and Development, CREST, Tokyo, Japan.
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30
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Masle-Farquhar E, Peters TJ, Miosge LA, Parish IA, Weigel C, Oakes CC, Reed JH, Goodnow CC. Uncontrolled CD21low age-associated and B1 B cell accumulation caused by failure of an EGR2/3 tolerance checkpoint. Cell Rep 2022; 38:110259. [DOI: 10.1016/j.celrep.2021.110259] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 11/03/2021] [Accepted: 12/21/2021] [Indexed: 11/28/2022] Open
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31
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Japp AS, Meng W, Rosenfeld AM, Perry DJ, Thirawatananond P, Bacher RL, Liu C, Gardner JS, Atkinson MA, Kaestner KH, Brusko TM, Naji A, Luning Prak ET, Betts MR. TCR +/BCR + dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes. Cell 2021; 184:827-839.e14. [PMID: 33545036 DOI: 10.1016/j.cell.2020.11.035] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 06/30/2020] [Accepted: 11/19/2020] [Indexed: 12/20/2022]
Abstract
Ahmed and colleagues recently described a novel hybrid lymphocyte expressing both a B and T cell receptor, termed double expresser (DE) cells. DE cells in blood of type 1 diabetes (T1D) subjects were present at increased numbers and enriched for a public B cell clonotype. Here, we attempted to reproduce these findings. While we could identify DE cells by flow cytometry, we found no association between DE cell frequency and T1D status. We were unable to identify the reported public B cell clone, or any similar clone, in bulk B cells or sorted DE cells from T1D subjects or controls. We also did not observe increased usage of the public clone VH or DH genes in B cells or in sorted DE cells. Taken together, our findings suggest that DE cells and their alleged public clonotype are not enriched in T1D. This Matters Arising paper is in response to Ahmed et al. (2019), published in Cell. See also the response by Ahmed et al. (2021), published in this issue.
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Affiliation(s)
- Alberto Sada Japp
- Department of Microbiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Wenzhao Meng
- Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Aaron M Rosenfeld
- Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Daniel J Perry
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA
| | - Puchong Thirawatananond
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA
| | - Rhonda L Bacher
- Department of Biostatistics, University of Florida, College of Medicine, Gainesville, FL 32610, USA
| | - Chengyang Liu
- Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Jay S Gardner
- Department of Microbiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
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- The Human Pancreas Analysis Program, Perelman School of Medicine, Philadelphia, PA 19104
| | - Mark A Atkinson
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA
| | - Klaus H Kaestner
- Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104
| | - Todd M Brusko
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA
| | - Ali Naji
- Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Eline T Luning Prak
- Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
| | - Michael R Betts
- Department of Microbiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
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32
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Abstract
Our understanding of the generation and function of B lymphocytes is well represented by publications in JEM, including numerous landmark studies on normal B cell immunology. This viewpoint reflects on a selection of such high-impact studies.
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Affiliation(s)
- Ralf Küppers
- Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical Faculty, Essen, Germany
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33
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Royster W, Wang P, Aziz M. The Role of Siglec-G on Immune Cells in Sepsis. Front Immunol 2021; 12:621627. [PMID: 33708213 PMCID: PMC7940683 DOI: 10.3389/fimmu.2021.621627] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 01/13/2021] [Indexed: 12/30/2022] Open
Abstract
Sepsis is a life-threatening clinical syndrome that results from an overwhelming immune response to infection. During sepsis, immune cells are activated by sensing pathogen-associated molecular patterns and damage-associated molecular patterns (DAMPs) through pattern recognizing receptors (PRRs). Regulation of the immune response is essential to preventing or managing sepsis. Sialic acid-binding immunoglobulin-type lectin-G (Siglec-G), a CD33 group of Siglec expressed in B-1a cells and other hematopoietic cells, plays an important immunoregulatory role. B-1a cells, a subtype of B lymphocytes, spontaneously produce natural IgM which confers protection against infection. B-1a cells also produce IL-10, GM-CSF, and IL-35 to control inflammation. Sialic acids are present on cell membranes, receptors, and glycoproteins. Siglec-G binds to the sialic acid residues on the B cell receptor (BCR) and controls BCR-mediated signal transduction, thereby maintaining homeostasis of Ca++ influx and NFATc1 expression. Siglec-G inhibits NF-κB activation in B-1a cells and regulates B-1a cell proliferation. In myeloid cells, Siglec-G inhibits DAMP-mediated inflammation by forming a ternary complex with DAMP and CD24. Thus, preserving Siglec-G’s function could be a novel therapeutic approach in sepsis. Here, we review the immunoregulatory functions of Siglec-G in B-1a cells and myeloid cells in sepsis. A clear understanding of Siglec-G is important to developing novel therapeutics in treating sepsis.
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Affiliation(s)
- William Royster
- Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, United States.,Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, United States.,Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, United States
| | - Ping Wang
- Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, United States.,Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, United States.,Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, United States
| | - Monowar Aziz
- Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, United States.,Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, United States
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34
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Jackson TR, Ling RE, Roy A. The Origin of B-cells: Human Fetal B Cell Development and Implications for the Pathogenesis of Childhood Acute Lymphoblastic Leukemia. Front Immunol 2021; 12:637975. [PMID: 33679795 PMCID: PMC7928347 DOI: 10.3389/fimmu.2021.637975] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 01/28/2021] [Indexed: 12/27/2022] Open
Abstract
Human B-lymphopoiesis is a dynamic life-long process that starts in utero by around six post-conception weeks. A detailed understanding of human fetal B-lymphopoiesis and how it changes in postnatal life is vital for building a complete picture of normal B-lymphoid development through ontogeny, and its relevance in disease. B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common cancers in children, with many of the leukemia-initiating events originating in utero. It is likely that the biology of B-ALL, including leukemia initiation, maintenance and progression depends on the developmental stage and type of B-lymphoid cell in which it originates. This is particularly important for early life leukemias, where specific characteristics of fetal B-cells might be key to determining how the disease behaves, including response to treatment. These cellular, molecular and/or epigenetic features are likely to change with age in a cell intrinsic and/or microenvironment directed manner. Most of our understanding of fetal B-lymphopoiesis has been based on murine data, but many recent studies have focussed on characterizing human fetal B-cell development, including functional and molecular assays at a single cell level. In this mini-review we will give a short overview of the recent advances in the understanding of human fetal B-lymphopoiesis, including its relevance to infant/childhood leukemia, and highlight future questions in the field.
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Affiliation(s)
- Thomas R Jackson
- Department of Paediatrics and MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
| | - Rebecca E Ling
- Department of Paediatrics and MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
| | - Anindita Roy
- Department of Paediatrics and MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.,National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, United Kingdom
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35
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Abstract
Patients with chronic lymphocytic leukemia can be divided into three categories: those who are minimally affected by the problem, often never requiring therapy; those that initially follow an indolent course but subsequently progress and require therapy; and those that from the point of diagnosis exhibit an aggressive disease necessitating treatment. Likewise, such patients pass through three phases: development of the disease, diagnosis, and need for therapy. Finally, the leukemic clones of all patients appear to require continuous input from the exterior, most often through membrane receptors, to allow them to survive and grow. This review is presented according to the temporal course that the disease follows, focusing on those external influences from the tissue microenvironment (TME) that support the time lines as well as those internal influences that are inherited or develop as genetic and epigenetic changes occurring over the time line. Regarding the former, special emphasis is placed on the input provided via the B-cell receptor for antigen and the C-X-C-motif chemokine receptor-4 and the therapeutic agents that block these inputs. Regarding the latter, prominence is laid upon inherited susceptibility genes and the genetic and epigenetic abnormalities that lead to the developmental and progression of the disease.
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MESH Headings
- Disease Progression
- Humans
- Immunotherapy
- Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis
- Leukemia, Lymphocytic, Chronic, B-Cell/etiology
- Leukemia, Lymphocytic, Chronic, B-Cell/genetics
- Leukemia, Lymphocytic, Chronic, B-Cell/therapy
- Mutation
- PAX5 Transcription Factor/metabolism
- Receptors, Antigen, B-Cell
- Signal Transduction
- Tumor Microenvironment
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Affiliation(s)
- Nicholas Chiorazzi
- The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York 11030, USA
| | - Shih-Shih Chen
- The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York 11030, USA
| | - Kanti R Rai
- The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York 11549, USA
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36
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Reis NFDC, Dupin TV, Costa CR, Toledo MDS, de Oliveira VC, Popi AF, Torrecilhas AC, Xander P. Leishmania amazonensis Promastigotes or Extracellular Vesicles Modulate B-1 Cell Activation and Differentiation. Front Cell Infect Microbiol 2020; 10:573813. [PMID: 33194814 PMCID: PMC7662559 DOI: 10.3389/fcimb.2020.573813] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 09/28/2020] [Indexed: 12/15/2022] Open
Abstract
B-1 cells are considered an innate-like B cell population that participates in effective innate and adaptive responses to pathogens. B-1 cells produce immunoglobulins, cytokines, chemokines, migrate to inflammatory sites, and differentiate into mononuclear phagocyte-like cells. Murine B-1 cells phagocytosed Leishmaniain vitro and in vivo and participate in immunity against Leishmania. Our group showed that B-1 cells or their extracellular vesicles (EVs) led to a resistance to experimental infection by L. amazonensis. However, the B-1 cells’ responses to Leishmania or EVs isolated from parasites are still poorly characterized. Studying the activation and differentiation of B-1 cells in vivo can contribute to a better understanding of how these cells participate in immunity to L. amazonensis. Thus, we evaluated the expression of myeloid (M-csfr, G-csfr, Spi-1) and lymphoid (EBF, E2A, IL-7R) lineage commitment factors, Toll-like receptors (TLRs), activation cell surface markers, nitric oxide (NO) and reactive oxygen species (ROS) production in murine peritoneal B-1 cells collected after 24 or 48 h post-infection with Leishmania (Leishmania) amazonensis promastigotes or EVs released by the parasites. Our results demonstrated that L. amazonensis infection did not stimulate the expression of CD40, CD80, CD86, F4/80, and MHC II in B-1 cells, but a significant decrease in the production of NO and ROS was observed. The infection induced a significantly higher arginase expression in B-1 cells, but the stimulation with EVs led to a decrease in this gene expression. TLR-2 and TLR-6 had significantly higher expression in B-1 cells from mice intraperitoneally stimulated with the parasite. The TLR-9 expression was higher in animals infected or stimulated for 48 h with EVs. Interestingly, in B-1 cells the stimulus with L. amazonensis led to a substantial increase in the expression of myeloid restricted transcription factors. Thus, our study suggests that the parasites or EVs differently modulated the activation and differentiation of B-1 cells.
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Affiliation(s)
- Natasha Ferraz de Campos Reis
- Laboratory of Cellular Immunology and Biochemistry of Fungi and Protozoa, Department of Pharmaceutical Sciences, Federal University of São Paulo, São Paulo, Brazil
| | - Talita Vieira Dupin
- Laboratory of Cellular Immunology and Biochemistry of Fungi and Protozoa, Department of Pharmaceutical Sciences, Federal University of São Paulo, São Paulo, Brazil
| | - Carolina Rizzaro Costa
- Laboratory of Cellular Immunology and Biochemistry of Fungi and Protozoa, Department of Pharmaceutical Sciences, Federal University of São Paulo, São Paulo, Brazil
| | - Maytê Dos Santos Toledo
- Laboratory of Cellular Immunology and Biochemistry of Fungi and Protozoa, Department of Pharmaceutical Sciences, Federal University of São Paulo, São Paulo, Brazil
| | - Vivian Cristina de Oliveira
- Department of Microbiology, Immunology and Parasitology, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil
| | - Ana Flavia Popi
- Department of Microbiology, Immunology and Parasitology, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil
| | - Ana Claudia Torrecilhas
- Laboratory of Cellular Immunology and Biochemistry of Fungi and Protozoa, Department of Pharmaceutical Sciences, Federal University of São Paulo, São Paulo, Brazil
| | - Patricia Xander
- Laboratory of Cellular Immunology and Biochemistry of Fungi and Protozoa, Department of Pharmaceutical Sciences, Federal University of São Paulo, São Paulo, Brazil
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37
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Papadopoulou M, Sanchez Sanchez G, Vermijlen D. Innate and adaptive γδ T cells: How, when, and why. Immunol Rev 2020; 298:99-116. [PMID: 33146423 DOI: 10.1111/imr.12926] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 09/03/2020] [Indexed: 12/13/2022]
Abstract
γδ T cells comprise the third cell lineage of lymphocytes that use, like αβ T cells and B cells, V(D)J gene rearrangement with the potential to generate a highly diverse T cell receptor (TCR) repertoire. There is no obvious conservation of γδ T cell subsets (based on TCR repertoire and/or function) between mice and human, leading to the notion that human and mouse γδ T cells are highly different. In this review, we focus on human γδ T cells, building on recent studies using high-throughput sequencing to analyze the TCR repertoire in various settings. We make then the comparison with mouse γδ T cell subsets highlighting the similarities and differences and describe the remarkable changes during lifespan of innate and adaptive γδ T cells. Finally, we propose mechanisms contributing to the generation of innate versus adaptive γδ T cells. We conclude that key elements related to the generation of the γδ TCR repertoire and γδ T cell activation/development are conserved between human and mice, highlighting the similarities between these two species.
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Affiliation(s)
- Maria Papadopoulou
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.,Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium.,ULB Center for Research in Immunology (U-CRI), Belgium
| | - Guillem Sanchez Sanchez
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.,Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium.,ULB Center for Research in Immunology (U-CRI), Belgium
| | - David Vermijlen
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.,Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium.,ULB Center for Research in Immunology (U-CRI), Belgium
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38
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Franke K, Pillai SY, Hoogenboezem M, Gijbels MJJ, Matlung HL, Geissler J, Olsman H, Pottgens C, van Gorp PJ, Ozsvar-Kozma M, Saito Y, Matozaki T, Kuijpers TW, Hendriks RW, Kraal G, Binder CJ, de Winther MPJ, van den Berg TK. SIRPα on Mouse B1 Cells Restricts Lymphoid Tissue Migration and Natural Antibody Production. Front Immunol 2020; 11:570963. [PMID: 33162986 PMCID: PMC7581795 DOI: 10.3389/fimmu.2020.570963] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/17/2020] [Indexed: 01/19/2023] Open
Abstract
The inhibitory immunoreceptor SIRPα is expressed on myeloid and neuronal cells and interacts with the broadly expressed CD47. CD47-SIRPα interactions form an innate immune checkpoint and its targeting has shown promising results in cancer patients. Here, we report expression of SIRPα on B1 lymphocytes, a subpopulation of murine B cells responsible for the production of natural antibodies. Mice defective in SIRPα signaling (SIRPαΔCYT mice) displayed an enhanced CD11b/CD18 integrin-dependent B1 cell migration from the peritoneal cavity to the spleen, local B1 cell accumulation, and enhanced circulating natural antibody levels, which was further amplified upon immunization with T-independent type 2 antigen. As natural antibodies are atheroprotective, we investigated the involvement of SIRPα signaling in atherosclerosis development. Bone marrow (SIRPαΔCYT>LDLR−/−) chimaeric mice developed reduced atherosclerosis accompanied by increased natural antibody production. Collectively, our data identify SIRPα as a unique B1 cell inhibitory receptor acting to control B1 cell migration, and imply SIRPα as a potential therapeutic target in atherosclerosis.
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Affiliation(s)
- Katka Franke
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | | | - Mark Hoogenboezem
- Sanquin Research and Landsteiner Laboratory, Department of Plasma Protein, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Marion J J Gijbels
- Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.,Department of Pathology, CARIM, Cardiovascular Research Institute Maastricht, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands
| | - Hanke L Matlung
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Judy Geissler
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Hugo Olsman
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Chantal Pottgens
- Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Patrick J van Gorp
- Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Maria Ozsvar-Kozma
- Department of Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
| | - Yasuyuki Saito
- Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takashi Matozaki
- Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Taco W Kuijpers
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.,Department of Pediatric Hematology, Immunology and Infectious Disease, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
| | - Rudi W Hendriks
- Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands
| | - Georg Kraal
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands
| | - Christoph J Binder
- Department of Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
| | - Menno P J de Winther
- Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.,Institute for Cardiovascular Prevention (IPEK), Munich, Germany
| | - Timo K van den Berg
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.,Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands
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39
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Liu Z, Liu Y, Li T, Wang P, Mo X, Lv P, Ge Q, Ma D, Han W. Cmtm7 knockout inhibits B-1a cell development at the transitional (TrB-1a) stage. Int Immunol 2020; 31:715-728. [PMID: 31081901 DOI: 10.1093/intimm/dxz041] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 05/11/2019] [Indexed: 01/19/2023] Open
Abstract
Innate-like B-1a cells are an important cell population for production of natural IgM and interleukin-10 (IL-10), and act as the first line against pathogens. We determined that CMTM7 is essential for B-1a cell development. Following Cmtm7 (CKLF-like MARVEL transmembrane domain-containing 7) knockout, B-1a cell numbers decreased markedly in all investigated tissues. Using a bone marrow and fetal liver adoptive transfer model and conditional knockout mice, we showed that the reduction of B-1a cells resulted from B-cell-intrinsic defects. Because of B-1a cell loss, Cmtm7-deficient mice produced less IgM and IL-10, and were more susceptible to microbial sepsis. Self-renewal and homeostasis of mature B-1a cells in Cmtm7-/- mice were not impaired, suggesting the effect of Cmtm7 on B-1a cell development. Further investigations demonstrated that the function of Cmtm7 in B-1a cell development occurred at the specific transitional B-1a (TrB-1a) stage. Cmtm7 deficiency resulted in a slow proliferation and high cell death rate of TrB-1a cells. Thus, Cmtm7 controls B-1a cell development at the transitional stage.
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Affiliation(s)
- Zhengyang Liu
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; NHC Key Laboratory of Medical Immunology, Beijing, China.,Peking University Center for Human Disease Genomics, Beijing, China
| | - Yuan Liu
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; NHC Key Laboratory of Medical Immunology, Beijing, China.,Peking University Center for Human Disease Genomics, Beijing, China
| | - Ting Li
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; NHC Key Laboratory of Medical Immunology, Beijing, China.,Peking University Center for Human Disease Genomics, Beijing, China
| | - Pingzhang Wang
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; NHC Key Laboratory of Medical Immunology, Beijing, China.,Peking University Center for Human Disease Genomics, Beijing, China
| | - Xiaoning Mo
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; NHC Key Laboratory of Medical Immunology, Beijing, China.,Peking University Center for Human Disease Genomics, Beijing, China
| | - Ping Lv
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; NHC Key Laboratory of Medical Immunology, Beijing, China.,Peking University Center for Human Disease Genomics, Beijing, China
| | - Qing Ge
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; NHC Key Laboratory of Medical Immunology, Beijing, China
| | - Dalong Ma
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; NHC Key Laboratory of Medical Immunology, Beijing, China.,Peking University Center for Human Disease Genomics, Beijing, China
| | - Wenling Han
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center; NHC Key Laboratory of Medical Immunology, Beijing, China.,Peking University Center for Human Disease Genomics, Beijing, China
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40
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Katayama N. Guest editorial: B1 cells: their ontogeny and malignant counterpart. Int J Hematol 2020; 111:619-621. [PMID: 32270389 DOI: 10.1007/s12185-020-02868-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 03/27/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Naoyuki Katayama
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
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41
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Xu X, Deobagkar-Lele M, Bull KR, Crockford TL, Mead AJ, Cribbs AP, Sims D, Anzilotti C, Cornall RJ. An ontogenetic switch drives the positive and negative selection of B cells. Proc Natl Acad Sci U S A 2020; 117:3718-3727. [PMID: 32019891 PMCID: PMC7035474 DOI: 10.1073/pnas.1915247117] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Developing B cells can be positively or negatively selected by self-antigens, but the mechanisms that determine these outcomes are incompletely understood. Here, we show that a B cell intrinsic switch between positive and negative selection during ontogeny is determined by a change from Lin28b to let-7 gene expression. Ectopic expression of a Lin28b transgene in murine B cells restored the positive selection of autoreactive B-1 B cells by self-antigen in adult bone marrow. Analysis of antigen-specific immature B cells in early and late ontogeny identified Lin28b-dependent genes associated with B-1 B cell development, including Arid3a and Bhleh41, and Lin28b-independent effects are associated with the presence or absence of self-antigen. These findings identify cell intrinsic and extrinsic determinants of B cell fate during ontogeny and reconcile lineage and selection theories of B cell development. They explain how changes in the balance of positive and negative selection may be able to adapt to meet the immunological needs of an individual during its lifetime.
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Affiliation(s)
- Xijin Xu
- Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom
| | - Mukta Deobagkar-Lele
- Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom
| | - Katherine R Bull
- Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom
| | - Tanya L Crockford
- Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom
| | - Adam J Mead
- Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom
| | - Adam P Cribbs
- Medical Research Council, Weatherall Institute of Molecular Medicine, Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom
| | - David Sims
- Medical Research Council, Weatherall Institute of Molecular Medicine, Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom
| | - Consuelo Anzilotti
- Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom
| | - Richard J Cornall
- Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom;
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42
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Wang Y, Liu J, Burrows PD, Wang JY. B Cell Development and Maturation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1254:1-22. [PMID: 32323265 DOI: 10.1007/978-981-15-3532-1_1] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Since the identification of B cells in 1965 (Cooper et al. 1965), three has been tremendous progress in our understanding of B cell development, maturation and function. A number of B cell subpopulations, including B-1, B-2 and regulatory B cells, have been identified. B-1 cells mainly originate from the fetal liver and contain B-1a and B-1b subsets. B-2 cells are derived from the bone marrow (BM) and can be further classified into follicular B (FOB) and marginal zone B (MZB) cells. Regulatory B cells (Bregs) function to suppress immune responses, primarily by production of the anti-inflammatory cytokine IL-10. B cell tolerance is established at several checkpoints, during B cell development in the BM (central tolerance) as well as during B cell maturation and activation in the periphery (peripheral tolerance). This chapter will focus on the regulation of important processes during the development and maturation of B-1 and B-2 cells.
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Affiliation(s)
- Ying Wang
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Jun Liu
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Peter D Burrows
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ji-Yang Wang
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
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43
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Kikushige Y. Pathophysiology of chronic lymphocytic leukemia and human B1 cell development. Int J Hematol 2019; 111:634-641. [PMID: 31797231 DOI: 10.1007/s12185-019-02788-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Revised: 11/28/2019] [Accepted: 11/28/2019] [Indexed: 12/22/2022]
Abstract
Chronic lymphocytic leukemia (CLL), the most frequent type of leukemia in adults, is a lymphoproliferative disease characterized by the clonal expansion of mature CD5+ B cells in peripheral blood, bone marrow, and secondary lymphoid tissues. Over the past decade, substantial advances have been made in understanding the pathogenesis of CLL, including the identification of recurrent mutations, and clarification of clonal architectures, transcriptome analyses, and the multistep leukemogenic process. The biology of CLL is now better understood. The present review focuses on recent insights into CLL leukemogenesis, emphasizing the role of genetic lesions, and the multistep process initiating from very immature hematopoietic stem cells. Finally, we also review progress in the study of human B1 B cells, the putative normal counterparts of CLL cells.
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Affiliation(s)
- Yoshikane Kikushige
- Department of Medicine and Biosystemic Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
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44
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Ontogeny of human B1 cells. Int J Hematol 2019; 111:628-633. [DOI: 10.1007/s12185-019-02775-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 10/28/2019] [Accepted: 10/29/2019] [Indexed: 12/31/2022]
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45
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da Rocha RFDB, LaRocque-de-Freitas IF, Arcanjo AF, Logullo J, Nunes MP, Freire-de-Lima CG, Decote-Ricardo D. B-1 Cells May Drive Macrophages Susceptibility to Trypanosoma cruzi Infection. Front Microbiol 2019; 10:1598. [PMID: 31338088 PMCID: PMC6629875 DOI: 10.3389/fmicb.2019.01598] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 06/26/2019] [Indexed: 12/16/2022] Open
Abstract
B-1 cells can directly and indirectly influence the immune response. These cells are known to be excellent producers of natural antibodies and can secrete a variety of immunomodulatory molecules. They are also able to differentiate into B-1 cell-derived phagocytes (B-1CDP). B-1 cells can modulate macrophages to become less effective, and B-1CDP cells are more susceptible in infection models. In this work, we investigated the microbicidal ability of these cells in Trypanosoma cruzi infection in vitro. The results show that macrophages from BALB/c mice are more susceptible to infection than macrophages from XID mice. The resistance observed in macrophages from XID mice was abolished in the presence of B-1 cells, and this event seems to be associated with IL-10 production by B-1 cells, which may have contributed to the decrease of NO production. Additionally, B-1CDP cells were more permissive to intracellular T. cruzi infection than peritoneal macrophages. These findings strongly suggest that B-1 cells and B-1CDP cells have a potential role in the persistence of the parasite in host cells.
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Affiliation(s)
| | | | - Angelica Fernandes Arcanjo
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Jorgete Logullo
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | - Debora Decote-Ricardo
- Instituto de Veterinária, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil
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46
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A population of CD20+CD27+CD43+CD38lo/int B1 cells in PNH are missing GPI-anchored proteins and harbor PIGA mutations. Blood 2019; 134:89-92. [DOI: 10.1182/blood.2019001343] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
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47
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Kobayashi M, Tarnawsky SP, Wei H, Mishra A, Azevedo Portilho N, Wenzel P, Davis B, Wu J, Hadland B, Yoshimoto M. Hemogenic Endothelial Cells Can Transition to Hematopoietic Stem Cells through a B-1 Lymphocyte-Biased State during Maturation in the Mouse Embryo. Stem Cell Reports 2019; 13:21-30. [PMID: 31231025 PMCID: PMC6626887 DOI: 10.1016/j.stemcr.2019.05.025] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Revised: 05/24/2019] [Accepted: 05/24/2019] [Indexed: 11/27/2022] Open
Abstract
Precursors of hematopoietic stem cells (pre-HSCs) have been identified as intermediate precursors during the maturation process from hemogenic endothelial cells to HSCs in the aorta-gonad-mesonephros (AGM) region of the mouse embryo at embryonic day 10.5. Although pre-HSCs acquire an efficient adult-repopulating ability after ex vivo co-culture, their native hematopoietic capacity remains unknown. Here, we employed direct transplantation assays of CD45-VE-cadherin(VC)+KIT+(V+K+) cells (containing pre-HSCs) into immunodeficient neonatal mice that permit engraftment of embryonic hematopoietic precursors. We found that freshly isolated V+K+ cells exhibited significantly greater B-1 lymphocyte-biased repopulating capacity than multilineage repopulating capacity. Additionally, B cell colony-forming assays demonstrated the predominant B-1 progenitor colony-forming ability of these cells; however, increased B-2 progenitor colony-forming ability emerged after co-culture with Akt-expressing AGM endothelial cells, conditions that support pre-HSC maturation into HSCs. Our studies revealed an unexpected B-1 lymphocyte bias of the V+K+ population and acquisition of B-2 potential during commitment to the HSC fate.
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Affiliation(s)
- Michihiro Kobayashi
- Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Stefan P Tarnawsky
- Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Haichao Wei
- Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Akansha Mishra
- Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Nathalia Azevedo Portilho
- Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Pamela Wenzel
- Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Brian Davis
- Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Jiaqian Wu
- Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Brandon Hadland
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Washington School of Medicine, Seattle, WA 98105, USA
| | - Momoko Yoshimoto
- Center for Stem Cell and Regenerative Medicine, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
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Novaes E Brito RR, Dos Santos Toledo M, Labussiere GM, Dupin TV, de Campos Reis NF, Perez EC, Xander P. B-1 cell response in immunity against parasites. Parasitol Res 2019; 118:1343-1352. [PMID: 30941496 DOI: 10.1007/s00436-019-06211-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 01/10/2019] [Indexed: 01/09/2023]
Abstract
The peritoneal cavity has a microenvironment capable of promoting proliferation, differentiation, and activation of the resident cells and recruitment of blood cells through the capillary network involved in the peritoneum. Among the cells found in the peritoneal cavity, B-1 cells are a particular cell type that contains features that are not very well defined. These cells differ from conventional B lymphocytes (B-2) by phenotypic, functional, and molecular characteristics. B-1 cells can produce natural antibodies, migrate to the inflammatory focus, and have the ability to phagocytose pathogens. However, the role of B-1 cells in immunity against parasites is still not completely understood. Several experimental models have demonstrated that B-1 cells can affect the susceptibility or resistance to parasite infections depending on the model and species. Here, we review the literature to provide information on the peculiarities of B-1 lymphocytes as well as their interaction with parasites.
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Affiliation(s)
| | - Mayte Dos Santos Toledo
- Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo Campus Diadema, Diadema, Brazil
| | | | - Talita Vieira Dupin
- Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo Campus Diadema, Diadema, Brazil
| | | | | | - Patricia Xander
- Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo Campus Diadema, Diadema, Brazil. .,Laboratório de Imunologia Celular e Bioquímica de Fungos e Protozoários, Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo campus Diadema, Rua São Nicolau, 210, Unidade José Alencar, Prédio de Pesquisa, 4° andar, Diadema, São Paulo, Brazil.
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Abstract
Oligodendrocytes generate myelin sheaths to promote rapid neurotransmission in the central nervous system (CNS). During brain development, oligodendrocyte precursor cells (OPCs) are generated in the medial ganglionic eminence, lateral ganglionic eminence, and dorsal pallium. OPCs proliferate and migrate throughout the CNS at the embryonic stage. After birth, OPCs differentiate into mature oligodendrocytes, which then insulate axons. Oligodendrocyte development is regulated by the extrinsic environment including neurons, astrocytes, and immune cells. During brain development, B lymphocytes are present in the meningeal space, and are involved in oligodendrocyte development by promoting OPC proliferation. T lymphocytes mediate oligodendrocyte development during the remyelination process. Moreover, a subset of microglia contributes to oligodendrocyte development during the neonatal periods. Therefore, the immune system, especially lymphocytes and microglia, contribute to oligodendrocyte development during brain development and remyelination.
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Affiliation(s)
- Shogo Tanabe
- Department of Molecular Neuroscience, World Premier International Immunology Frontier Research Center, Osaka University, Suita-shi, Osaka, Japan
| | - Toshihide Yamashita
- Department of Molecular Neuroscience, World Premier International Immunology Frontier Research Center, Osaka University, Suita-shi, Osaka, Japan.,Graduate School of Medicine, Osaka University, Suita-shi, Osaka, Japan.,Graduate School of Frontier Biosciences, Osaka University, Suita-shi, Osaka, Japan
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Abstract
B-1 cells represent an innate-like early-developing B cell population, whose existence as an independent lymphocyte subset has been questioned in the past. Recent molecular and lineage tracing studies have not only confirmed their unique origins and differentiation paths, they have also provided a rationale for their distinctive functionalities compared to conventional B cells. This review summarizes our current understanding of B-1 cell development, and the activation events that regulate B-1 cell responses to self and foreign antigens. We discuss the unresolved question to what extent BCR engagement, that is, antigen-specificity versus innate signaling contributes to B-1 cell's participation in tissue homeostasis and immune defense as providers of 'natural' and antigen-induced antibody responses, and as cytokine-producing immune regulators.
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