• Non-malignant B cells
• TME
• hematologic malignancies

• Humans
• B-Lymphocytes/immunology
• B-Lymphocytes/pathology
• B-Lymphocytes/metabolism
• Hematologic Neoplasms/immunology
• Hematologic Neoplasms/pathology
• Hematologic Neoplasms/metabolism
• Tumor Microenvironment/immunology
• Animals

• Humans
• Animals
• B-Lymphocytes/immunology
• B-Lymphocytes/metabolism
• Neoplasms/immunology
• Neoplasms/metabolism
• Autoimmunity/immunology
• Autoimmune Diseases/immunology
• Autoimmune Diseases/metabolism
• Energy Metabolism/immunology
• Metabolic Networks and Pathways/immunology

• Alzheimer's disease
• B cell
• adaptive immunity
• amyloid-β
• immunotherapy
• tau

• B-cell development
• BCR
• Cell cycle
• MAPK
• Pim1

• Animals
• Proto-Oncogene Proteins c-pim-1/metabolism
• Proto-Oncogene Proteins c-pim-1/genetics
• B-Lymphocytes/immunology
• B-Lymphocytes/metabolism
• Mice
• T-Lymphocytes/immunology
• T-Lymphocytes/metabolism
• Cell Proliferation
• Receptors, Antigen, B-Cell/metabolism
• Receptors, Antigen, B-Cell/genetics
• Mice, Knockout
• MAP Kinase Signaling System
• Cyclin-Dependent Kinase 2/metabolism
• Cyclin-Dependent Kinase 2/genetics
• Cyclin B1/metabolism
• Cyclin B1/genetics
• Mitogen-Activated Protein Kinases/metabolism
• Mitogen-Activated Protein Kinases/genetics
• Cyclin E/metabolism
• Cyclin E/genetics
• Mice, Inbred C57BL
• Oncogene Proteins

• allergen immunotherapy
• allergic rhinitis
• asthma
• atopic dermatitis
• food allergy
• immune system
• regulatory B cells

• Fluzone vaccine
• adults
• humoral response
• influenza
• memory B-cells

• Humans
• Influenza Vaccines/immunology
• Antibodies, Viral/blood
• Antibodies, Viral/immunology
• Influenza A Virus, H1N1 Subtype/immunology
• Influenza, Human/immunology
• Influenza, Human/prevention & control
• Male
• Adult
• Female
• Memory B Cells/immunology
• Vaccines, Inactivated/immunology
• Vaccination
• Middle Aged
• B-Lymphocytes/immunology
• Young Adult
• Immunologic Memory
• Hemagglutination Inhibition Tests
• Hemagglutinin Glycoproteins, Influenza Virus/immunology
• Immunoglobulin G/blood
• Immunoglobulin G/immunology
• Immunoglobulin M/immunology
• Immunoglobulin M/blood
• Adolescent

• National Institutes of Health
• Cleveland Clinic Foundation

• B cells
• CD21low cells
• EBUS-TBNA
• class-switched memory B cells
• lung cancer
• lymph nodes
• sarcoidosis

• Humans
• Sarcoidosis/immunology
• Sarcoidosis/pathology
• Lung Neoplasms/immunology
• Lung Neoplasms/pathology
• B-Lymphocyte Subsets/pathology
• Lymph Nodes/pathology
• Flow Cytometry
• Leukocytes/pathology
• Cell Differentiation
• Male
• Female
• Adult
• Middle Aged
• Aged
• Immunological Memory Cells/pathology

• statutory grant number 608 Military Institute of Medicine-National Research Institute

• B cells
• B-cell receptor
• BCR signaling
• Lrba
• NF-κB
• Plcγ2
• p50 activation

• Animals
• Mice
• Adaptor Proteins, Signal Transducing/genetics
• Adaptor Proteins, Signal Transducing/metabolism
• B-Lymphocytes/immunology
• B-Lymphocytes/metabolism
• Lipopolysaccharides
• Lymphocyte Activation/immunology
• Mice, Inbred C57BL
• Mice, Knockout
• NF-kappa B/metabolism
• Receptors, Antigen, B-Cell/metabolism
• Signal Transduction

• Instituto Nacional de Pediatria

• Covid-19
• Cytokine Storm
• Immune suppression
• Macrophage polarization

• Humans
• COVID-19
• SARS-CoV-2
• Cytokine Release Syndrome
• T-Lymphocytes
• Immunity

• Allergic asthma
• B cells
• Childhood asthma
• Immune system
• Regulatory B cells

• SCHA 997/10-1 (CK) and DFG SCHA 997/11-1 (BS). DFG

• Humans
• Hepatitis B Vaccines
• Programmed Cell Death 1 Receptor
• Health Personnel

• 21740 Shiraz University of Medical Sciences

• B cells
• RNAseq analysis
• VirScan
• mitochondria
• viral infection

• National Institutes of Health

• B-cells
• T-cells
• adaptive immune system
• miRNA
• signaling pathway mediators

• B cells
• Sphingosine-1-phosphate
• abdominal sepsis
• antibody production
• germinal center reaction
• spleen

• Mice
• Animals
• Antibody Formation
• Lysophospholipids/metabolism
• Germinal Center/metabolism
• Antigens
• Sepsis

• B cells
• TIL-B
• antigen presentation
• antigen processing
• cellular therapies
• professional APC

• Cell Proliferation/genetics
• MicroRNAs/metabolism
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Receptors, Interleukin-7/genetics

• Austrian Science Fund

The transcriptional regulation of B-cell response to antigen stimulation is complex and involves an intricate network of dynamic signals from cytokines and transcription factors propagated from T-cell interaction. Long-term alloimmunity, in the setting of organ transplantation, is dependent on this B-cell response, which does not appear to be halted by current immunosuppressive regimens which are targeted at T cells. There is emerging evidence that shows that B cells have a diverse response to solid organ transplantation that extends beyond plasma cell antibody production. In this review, we discuss the mechanistic pathways of B-cell activation and differentiation as they relate to the transcriptional regulation of germinal center B cells, plasma cells, and memory B cells in the setting of solid organ transplantation.

• B-Lymphocytes
• Germinal Center
• Graft Rejection
• Histocompatibility
• Organ Transplantation

• CP: Immunology
• IL-4
• autoimmunity
• innate help
• polyreactive antibodies
• transitional B cells
• γδ T cells

• B cell
• Breg
• antibody
• immunogenomics
• tertiary lymphoid structure
• tumor microenvironment

The Integrity model proposes that the adaptive immune response defends, protects and keeps vigilance over the unity of an organism. These functions conceptually rely on three signals that can explain them. All signals have a dual character. The signal‐1 is the recognition of antigen or peptide/MHC ligand. The signal‐2 comprises either help and costimulation or suppression and coinhibition. Lastly, the signal‐3 signals tissues' condition, state or integrity. A part overlaps with the Danger‐associated molecular patterns, and the other part should be detected by putative cell‐surface molecules, intracellular factors or epigenetic events. They are called the Integrity‐associated molecular patterns (IAMPs). The IAMPs originate from damaged (positive signal‐3) or undamaged (negative signal‐3) tissues. The positive signal‐3 would induce costimulatory signal‐2, whereas the negative signal‐3 would induce coinhibitory signal‐2 in APCs. However, in analogue reality, we might more likely encounter a range of signals supposedly sensed by a group of responder cells and integrated overtime (quorum sensing). The predominant option would sway the decision of the immune system to perform either defence or protection (active tolerance). Thus, the quorum sensing supposedly delivers two qualitative thresholds for T (and B) cells' decisions to defend or suppress. If these were not attained, the vigilance (anergy) of adaptive immunocytes for T‐dependent antigens would ensue. These functions provide defence against pathogens and preservation of unity/integrity of an organism, which in turn permits protection of commensals.

• adaptive immunity
• hypothesis
• innate immunity
• natural selection

Most of the membrane molecules involved in immune response are glycosylated. N-glycans linked to asparagine (Asn) of immune molecules contribute to the protein conformation, surface expression, stability, and antigenicity. Core fucosylation catalyzed by core fucosyltransferase (FUT8) is the most common post-translational modification. Core fucosylation is essential for evoking a proper immune response, which this review aims to communicate. First, FUT8 deficiency suppressed the interaction between μHC and λ5 during pre-BCR assembly is given. Second, we described the effects of core fucosylation in B cell signal transduction via BCR. Third, we investigated the role of core fucosylation in the interaction between helper T (T_H) cells and B cells. Finally, we showed the role of FUT8 on the biological function of IgG. In this review, we discussed recent insights into the sites where core fucosylation is critical for humoral immune responses.

• Fucose/metabolism
• Fucosyltransferases
• Glycosylation
• Immunity, Humoral
• Immunoglobulin G

• National Natural Science Foundation of China

Btk and Vav proteins are all components of the signalosome that builds upon B cell receptor (BCR) activation. However, the role of Vav proteins within the signalosome is quite complex and not yet fully understood. Until now, studies of these have focused predominantly on a deficiency of Vav proteins alone or in combination with other Vav protein family members. Since a physical association of Btk with Vav was shown previously, we asked whether these molecules lie in the same or independent signaling pathways. By analyzing Vav1 and Vav3 single knock-out mice and generating double-knock-out animals deficient for either Vav1 or Vav3 and Btk, we observed, in line with previous publications, no severe B cell developmental defects when either Vav1 or Vav3 alone are not expressed. However, a simultaneous deficiency of Btk together with either Vav1 or Vav3 leads to a severe reduction of splenic B cells, which exhibit an immature phenotype. B cell developmental defects of Btk/Vav1-double deficient mice in the periphery were more severe than those observed in Btk-single-deficient animals. Additionally, morphological changes in splenic microarchitecture were observed in double- but also in single-knock-out mutants. These observations were accompanied by reduced BCR-induced Ca²⁺ mobilization, proliferation, germinal center formation and immunoglobulin secretion. Although deletion of Btk alone impaired Ca²⁺ mobilization upon BCR activation, the defect was even more severe when Vav1 or Vav3 were also mutated, indicating that Btk and the Vav proteins act in separate pathways that converge on Ca2+ signaling. In vitro ASC differentiation suggests that both B and T cells contribute to the observed phenotype of a Btk/Vav-double deficiency. Our results show that Vav proteins and Btk are both components of the BCR-activated signalosome but control separate signaling pathways important for B cell development.

Given the importance of B lymphocytes in inflammation and immune defense against pathogens, mice transgenic for Cre under the control of Cd19 promoter (Cd19^Cre/+ mice) have been widely used to specifically investigate the role of loxP-flanked genes in B cell development/function. However, impacts of expression/insertion of the Cre transgene on the phenotype and function of B cells have not been carefully studied. Here, we show that the number of marginal zone B and B1a cells was selectively reduced in Cd19^Cre/+ mice, while B cell development in the bone marrow and total numbers of peripheral B cells were comparable between Cd19^Cre/+ and wild type C57BL/6 mice. Notably, humoral responses to both T cell-dependent and independent antigens were significantly increased in Cd19^Cre/+ mice. We speculate that these differences are mainly attributable to reduced surface CD19 levels caused by integration of the Cre-expressing cassette that inactivates one Cd19 allele. Moreover, our literature survey showed that expression of Cd19^Cre/+ alone may affect the development/progression of inflammatory and anti-infectious responses. Thus, our results have important implications for the design and interpretation of results on gene functions specifically targeted in B cells in the Cd19^Cre/+ mouse strain, for instance, in the context of (auto) inflammatory/infectious diseases.

• Animals
• Antibodies/metabolism
• Antigens, CD19/metabolism
• B-Lymphocytes
• Integrases
• Mice
• Mice, Inbred C57BL
• Phenotype

• CAR-T therapy
• COVID-19
• Cellular immunity
• Hematopoietic cell transplantation
• Humoral immunity
• Immunocompromised
• Neutralizing antibodies
• SARS-CoV-2
• Vaccine response
• mRNA vaccine

• COVID-19
• COVID-19 Vaccines
• Cell- and Tissue-Based Therapy
• Humans
• Neoplasm Recurrence, Local
• Receptors, Chimeric Antigen
• SARS-CoV-2

• B cell activating factor
• proliferation-inducing ligand
• therapy

• B cell
• biliary atresia
• liver
• liver diseases
• liver fibrosis
• paediatric liver disease

• Age Factors
• Animals
• B-Lymphocytes/drug effects
• B-Lymphocytes/immunology
• B-Lymphocytes/metabolism
• Cell Differentiation
• Humans
• Immunomodulating Agents/therapeutic use
• Liver/drug effects
• Liver/immunology
• Liver/metabolism
• Liver/pathology
• Liver Diseases/immunology
• Liver Diseases/metabolism
• Liver Diseases/pathology
• Liver Diseases/therapy
• Lymphocyte Depletion
• Phenotype
• Rituximab/therapeutic use
• Signal Transduction

• NC/R002061/1 National Centre for the Replacement, Refinement and Reduction of Animals in Research
• MRF_MRF-169-0001-F-STAM-C0826 MRF
• MR/M007669/1 Medical Research Council
• MC_PC_16037 Medical Research Council
• Wellcome Trust
• 108871/B/15/Z Wellcome Trust
• UK Research and Innovation
• Wellcome
• European Federation of Pharmaceutical Industries and Associations

• IgA
• ageing
• gut microbiome
• multiple sclerosis
• neurodegeneration

• Animals
• Central Nervous System Diseases/immunology
• Gastrointestinal Microbiome/immunology
• Humans
• Immunoglobulin A/immunology
• Neuroimmunomodulation/immunology
• Neuroinflammatory Diseases/immunology

• B lymphocyte
• adaptive immunity
• cardiac injury
• heart failure
• innate immunity
• vascular disease

• Bregs
• Tfh
• Tfr
• alloantibodies
• tolerant B cells
• transplant tolerance
• transplantation

• P01 AI056299 NIAID NIH HHS
• R01 AI153124 NIAID NIH HHS
• R01 AI142747 NIAID NIH HHS
• P01 AI097113 NIAID NIH HHS
• R01 AI148705 NIAID NIH HHS

• COVID-19 vaccine
• Immunologic memory
• PPAR

Loss of B cell tolerance is central to autoimmune diseases such as systemic lupus erythematosus (SLE). As such, the mechanisms involved in B cell development, maturation, activation, and function that are aberrantly regulated in SLE are of interest in the design of targeted therapeutics. While many factors are involved in the generation and regulation of B cell responses, miRNAs have emerged as critical regulators of these responses within the last decade. To date, miRNA involvement in B cell responses has largely been studied in non-autoimmune, immunization-based systems. However, miRNA profiles have also been strongly associated with SLE in human patients and these molecules have proven critical in both the promotion and regulation of disease in mouse models and in the formation of autoreactive B cell responses. Functionally, miRNAs are small non-coding RNAs that bind to complementary sequences located in target mRNA transcripts to mediate transcript degradation or translational repression, invoking a post-transcriptional level of genetic regulation. Due to their capacity to target a diverse range of transcripts and pathways in different immune cell types and throughout the various stages of development and response, targeting miRNAs is an interesting potential therapeutic avenue. Herein, we focus on what is currently known about miRNA function in both normal and SLE B cell responses, primarily highlighting miRNAs with confirmed functions in mouse models. We also discuss areas that should be addressed in future studies and whether the development of miRNA-centric therapeutics may be a viable alternative for the treatment of SLE.

• B cells
• autoimmunity
• germinal center
• miRNA
• systemic lupus erythematosus

• Crohn disease
• TNFα inhibitor
• children
• transitional B cells
• ulcerative colitis

• B-cell activation
• PD-1
• marginal zone (MZ) B cell
• plasmablasts
• transitional B cell

• epigenetics
• multiple myeloma
• plasma cell differentiation
• polycomb

• Animals
• Cell Differentiation
• Hematopoiesis
• Humans
• Neoplasms/immunology
• Neoplasms/metabolism
• Neoplasms/pathology
• Plasma Cells/immunology
• Plasma Cells/metabolism
• Plasma Cells/pathology
• Polycomb-Group Proteins/metabolism

The naive heart harbors a population of intravascular B cells that make close contact with the cardiac microvasculature. However, the timing of their appearance and their organ specificity remain unknown. To address this knowledge gap, we performed a systematic analysis of B cells isolated from the myocardium and other organs, from embryonic life to adulthood. We found that the phenotype of myocardial B cells changed dynamically during development. While neonatal heart B cells were mostly CD11b⁺ and CD11b^– CD21^–CD23^–, adult B cells were predominantly CD11b^–CD21⁺CD23⁺. Histological analysis and intravital microscopy of lung and liver showed that organ-associated B cells in contact with the microvascular endothelium were not specific to the heart. Flow cytometric analysis of perfused hearts, livers, lungs, and spleen showed that the dynamic changes in B cell subpopulations observed in the heart during development mirrored changes observed in the other organs. Single cell RNA sequencing (scRNAseq) analysis of B cells showed that myocardial B cells were part of a larger population of organ-associated B cells that had a distinct transcriptional profile. These findings broaden our understanding of the biology of myocardial-associated B cells and suggest that current models of the dynamics of naive B cells during development are incomplete.

Myocardial B cells are part of a larger population of intravascular organ-associated B cells.

• B cells
• Cardiology
• Immunology

Indoleamine-2,3-dioxygenase (IDO)1 and IDO2 are two closely related tryptophan catabolizing enzymes encoded by linked genes. The IDO pathway is also immunomodulatory, with IDO1 well-characterized as a mediator of tumor immune evasion. Due to its homology with IDO1, IDO2 has been proposed to have a similar immunoregulatory function. Indeed, IDO2, like IDO1, is necessary for the differentiation of regulatory T cells in vitro. However, compared to IDO1, in vivo studies demonstrated a contrasting role for IDO2, with experiments in preclinical models of autoimmune arthritis establishing a proinflammatory role for IDO2 in mediating B and T cell activation driving autoimmune disease. Given their potentially opposing roles in inflammatory responses, interpretation of results obtained using IDO1 or IDO2 single knockout mice could be complicated by the expression of the other enzyme. Here we use IDO1 and IDO2 single and double knockout (dko) mice to define the differential roles of IDO1 and IDO2 in B cell-mediated immune responses. Autoreactive T and B cell responses and severity of joint inflammation were decreased in IDO2 ko, but not IDO1 ko arthritic mice. Dko mice had a reduction in the number of autoantibody secreting cells and severity of arthritis: however, percentages of differentiated T cells and their associated cytokines were not reduced compared to IDO1 ko or wild-type mice. These data suggest that autoreactive B cell responses are mediated by IDO2, while autoreactive T cell responses are indirectly affected by IDO1 expression in the IDO2 ko mice. IDO2 also influenced antibody responses in models of influenza infection and immunization with T cell-independent type II antigens. Taken together, these studies provide evidence for the contrasting roles IDO1 and IDO2 play in immune responses, with IDO1 mediating T cell suppressive effects and IDO2 working directly in B cells as a proinflammatory mediator of B cell responses.

• B cells
• experimental arthritis
• immunization
• influenza
• murine model

• bone marrow microenvironment (BMME)
• long-lived plasma cell (LLPC)
• multiple myeloma (MM)

B‐cells are essential in the defense against Mycobacterium tuberculosis. Studies on isolated cells may not accurately reflect the responses that occur in vivo due to the presence of other cells. This study elucidated the influence of microenvironment complexity on B‐cell polarization and function in the context of tuberculosis disease.

B‐cell function was tested in whole blood, peripheral blood mononuclear cells (PBMCs), and as isolated cells. The different fractions were stimulated and the B‐cell phenotype and immunoglobulin profiles analyzed.

The immunoglobulin profile and developmental B‐cell frequencies varied for each of the investigated sample types, while in an isolated cellular environment, secretion of immunoglobulin isotypes immunoglobulin A (IgA), IgG2, and IgG3 was hampered. The differences in the immunoglobulin profile highlight the importance of cell‐cell communication for B‐cell activation. Furthermore, a decrease in marginal zone B‐cell frequencies and an increase in T1 B‐cells was observed following cell isolation, indicating impaired B‐cell development in response to in vitro antigenic stimulation in isolation.

Our results suggest that humoral B‐cell function and development was impaired likely due to a lack of costimulatory signals from other cell types. Thus, B‐cell function should ideally be studied in a PBMC or whole blood fraction.

• B cells
• IgG, PBMC
• M. tuberculosis
• microenvironment