Sepsis, a leading cause of death in intensive care units, is associated with immune alterations that increase the patients' risk of secondary infections and mortality, so better understandings of the pathophysiology of sepsis-induced immunosuppression is essential for the development of therapeutic strategies. In a murine model of sepsis that recapitulates immune alterations observed in patients, here we demonstrate that PD-L1+CD44+B220LowCD138+IgM+ regulatory plasma cells are induced in spleen and regulate ex vivo proliferation and IFNɣ secretion induced by stimulation of T splenocytes. This effect is mediated both by cell-cell contact through increased PD-L1 expression on plasma cells and by production of a soluble factor. These observations are recapitulated in three cohorts of critically ill patients with bacterial and viral sepsis in association with increased mortality. Our findings thus reveal the function of regulatory plasma cells in the pathophysiology of sepsis-induced immune alterations, and present a potential therapeutic target for improving immune cell function impaired by sepsis.

This study aimed to investigate the immunogenicity of the hepatitis B virus (HBV) vaccine by applying a normal and high-dose hepatitis B virus vaccination program in the mice modeling of non-alcoholic fatty liver disease (NAFLD). NAFLD was induced in mouse livers via diet. At the 10-week mark, both groups were divided into 3 subgroups. While the standard dose vaccination program was applied on days 0, 7, and 21, two high-dose programs were applied: one was applied on days 0 and 7, and the other was applied on days 0, 7, and 21. All mice were euthanized. Blood samples from anti-HB titers; T follicular helper, T follicular regulatory, CD27+, and CD38+ cells; and the liver, spleen, and thymus were taken for histopathologic evaluation. NAFLD subgroups receiving high doses showed higher hepatocyte ballooning scores than normal-dose subgroup. There were differences in CD27+ and CD27+CD38+ cells in animals fed on different diets, without any differences or interactions in terms of vaccine protocols. In the NAFLD group, a negative correlation was observed between anti-HB titers and T helper and CD27+ cells, while a positive correlation was observed with CD38+ cells. NAFLD induced changes in immune parameters in mice, but there was no difference in vaccine efficacy among the applied vaccine protocols. Based on this study's results, high-dose vaccination protocols are not recommended in cases of NAFLD, as they do not enhance efficacy and may lead to increased liver damage.

The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB.

We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups.

The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042).

After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Following infection and vaccination against SARS-CoV-2, humoral components of the adaptive immune system play a key role in protecting the host. Specifically, B cells generate high-affinity antibodies against various antigens of the virus. In this review, we discuss the mechanisms of immunity initiation through both natural infection and vaccination, shedding light on the activation of B cell subsets in response to SARS-CoV-2 infection and vaccination. The innate immune system serves as the initial line of primary and nonspecific defence against viruses. However, within several days following infection or a vaccine dose, a virus-specific immune response is initiated, primarily by B cells that produce antibodies. These antibodies contribute to the resolution of the disease. Subsequently, these B cells transition into memory B cells, which play a crucial role in providing long-term immunity against the virus. CD4+ T helper cells initiate a cascade, leading to B cell somatic hypermutation, germinal center memory B cells, and the production of neutralizing antibodies. B-cell dysfunction can worsen disease severity and reduce vaccine efficacy. Notably, individuals with B cell immunodeficiency show lower IL-6 production. Furthermore, this review delves into several aspects of immune responses, such as hybrid immunity, which has shown promise in boosting broad-spectrum protection. Cross-reactive immunity is under scrutiny as well, as pre-existing antibodies can offer protection against the disease. We also decipher breakthrough infection mechanisms, especially with the novel variants of the virus. Finally, we discuss some potential therapeutic solutions regarding B cells including convalescent plasma therapy, B-1 cells, B regulatory cell (Breg) modulation, and the use of neutralizing monoclonal antibodies in combating the infection. Ongoing research is crucial to grasp population immunity trends and assess the potential need for booster doses in maintaining effective immune responses against potential viral threats.

B lymphocytes play a vital role in the human defense against viral infections by producing specific antibodies. They are also critical for the prevention of infectious diseases by vaccination, and their activation influences the efficacy of the vaccination. Since the beginning of coronavirus disease 2019 (COVID-19), which became the main concern of the world health system, many efforts have been made to treat and prevent the disease. However, for the development of successful therapeutics and vaccines, it is necessary to understand the interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, and the immune system. The innate immune system provides primary and nonspecific defense against the virus, but within several days after infection, a virus-specific immune response is provided first by antibody-producing B cells, which are converted after the resolution of disease to memory B cells, which provide long-term immunity. Although a failure in B cell activation or B cell dysfunction can cause a severe form of the disease and also lead to vaccination inefficiency, some individuals with B cell immunodeficiency have shown less production of the cytokine IL-6, resulting in a better disease outcome. In this review, we present the latest findings on the interaction between SARS-CoV-2 and B lymphocytes during COVID-19 infection.

The cellular mechanisms involved in the lack of protective antibody response after hepatitis B vaccination are still rather unclear. Regulatory B cells (Breg) known as modulators of B-and T-cell responses may contribute to poor vaccine responsiveness. The current study aimed to investigate the role of regulatory B cells (Breg) in hepatitis B vaccine non-responsiveness after immunization with second- or third-generation hepatitis B vaccines.

We performed comparative phenotypic and frequency analysis of Breg subsets (CD24⁺CD27⁺ and CD24^highCD38^high Breg) in second-generation hepatitis B vaccine non-responders (2^nd HBvac NR, n = 11) and responders (2^nd HBvac R, n = 8) before (d0), on day 7 (d7), and 28 (d28) after booster vaccination. Cryopreserved peripheral blood mononuclear cells were stimulated ex vivo with a combination of CpG, PMA, and Ionomycin (CpG+P/I) and analyzed for numbers and IL-10 expression levels of Breg by flow cytometry-based analyses.

Flow cytometry-based analyses revealed elevated frequencies of CD24⁺CD27⁺ Breg at all time points and significantly higher frequencies of CD24^highCD38^high Breg on d0 (p = 0.004) and 28 (p = 0.012) in 2^nd HBvac NR compared to 2^nd HBvac R. In parallel, we observed significantly lower levels of CpG+P/I-induced IL-10 expression levels of CD24⁺CD27⁺ and CD24^highCD38^high Breg (d0: p < 0.0001; d7: p = 0.0004; d28: p = 0.0003 and d0: p = 0.016; d7: p = 0.016, respectively) in 2^nd HBvac NR compared to 2^nd HBvac R before and after booster immunization. Frequencies of CD24⁺CD27⁺ and CD24^highCD38^high Breg significantly decreased after third-generation hepatitis B booster vaccination (d7: p = 0.014; d28: p = 0.032 and d7: p = 0.045, respectively), whereas IL-10 expression levels of both Breg subsets remained stable.

Here we report significantly higher frequencies of CD24^highCD38^high Breg in parallel with significantly lower IL-10 expression levels of CD24⁺CD27⁺ and CD24^highCD38^high Breg in 2^nd HBvac NR compared to 2^nd HBvac R. Anti-HBs seroconversion accompanied by a decrease of Breg numbers after booster immunization with a third-generation hepatitis B vaccine could indicate a positive effect of third-generation hepatitis B vaccines on Breg-mediated immunomodulation in hepatitis B vaccine non-responders.

Helicobacter pylori (H. pylori) is a gram-negative which can cause several gastroduodenal diseases, including gastritis and peptic ulcer disease (PUD). H. pylori specific genotypes have been related to increased occurrence of gastritis and PUD. The aim of this study was to investigate the clinical relevance of the major virulence factors of H. pylori with clinical outcomes and histological parameters in Iranian patients. Totally, 200 subjects with PUD and gastritis disease who underwent gastroduodenal endoscopy were enrolled in this study. The presence of the cagA, vacA, oipA, babA2, and iceA genes in antral gastric biopsy specimens were determined by polymerase chain reaction (PCR) and the results were compared with clinical outcomes and histological parameters. The frequency of babA2 ⁺ , oipA ⁺ , vacA s1/m2, and vacA m2 genes was significantly higher in patients with peptic ulcer disease compared with patients with gastritis. In contrast, the frequency of vacA s1/m1 gene was significantly higher in gastritis subjects than PUD subjects. The high-density scores of H. pylori were strongly associated with iceA1 ^¯ , babA2 ⁺ , and oipA ⁺ genes. Additionally, the high polymorphonuclear cell infiltration and high mononuclear cell infiltration scores were strongly associated with the cagA ⁺ , iceA1 ^¯ , oipA ⁺ genes and cagA ⁺ , babA2 ⁺ , oipA ⁺ genes, respectively. Our study indicated that the vacA, babA2, and oipA virulence factors are related to a higher risk of PUD in subjects with H. pylori-infection. Infection with these strains was associated with a more severe gastropathy.