Although IL-10-producing regulatory B cells (Bregs) play important roles in immune regulation, their surface phenotypes and functional characteristics have not been fully investigated. In this study, we report that the frequency of IL-10-producing Bregs in human peripheral blood, spleens, and tonsils is similar, but they display heterogenous surface phenotypes. Nonetheless, CD24 hi CD38 hi transitional B cells (TBs) and CD24 hi CD27 + B cells (human equivalent of murine B10 cells) are the major IL-10producing B cells. They both suppress CD4 + T cell proliferation as well as IFN-g/IL-17 expression. However, CD24 hi CD27 + B cells were more efficient than TBs at suppressing CD4 + T cell proliferation and IFN-g/IL-17 expression, whereas they both coexpress IL-10 and TNF-a. TGF-b1 and granzyme B expression were also enriched within CD24 hi CD27 + B cells, when compared with TBs. Additionally, CD24 hi CD27 + B cells expressed increased levels of surface integrins (CD11a, CD11b, a1, a4, and b1) and CD39 (an ecto-ATPase), suggesting that the in vivo mechanisms of action of the two Breg subsets are not the same. Lastly, we also report that liver allograft recipients with plasma cell hepatitis had significant decreases of both Breg subsets.

The new epidemic Middle East Respiratory Syndrome (MERS) is caused by a type of human coronavirus called MERS-CoV which has global fatality rate of about 30%. We are investigating potential antiviral therapeutics against MERS-CoV by using host microRNAs (miRNAs) which may downregulate viral gene expression to quell viral replication. We computationally predicted potential 13 cellular miRNAs from 11 potential hairpin sequences of MERS-CoV genome. Our study provided an interesting hypothesis that those miRNAs, that is, hsa-miR-628-5p, hsa-miR-6804-3p, hsa-miR-4289, hsa-miR-208a-3p, hsa-miR-510-3p, hsa-miR-18a-3p, hsa-miR-329-3p, hsa-miR-548ax, hsa-miR-3934-5p, hsa-miR-4474-5p, hsa-miR-7974, hsa-miR-6865-5p, and hsa-miR-342-3p, would be antiviral therapeutics against MERS-CoV infection.

Regulatory B cells (Bregs) contribute to immune regulation. However, the mechanisms of action of Bregs remain elusive. Here, we report that T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on human memory B cells especially CD19+CD24hiCD27+CD39hiIgD−IgM+CD1c+ B cells is essential for effective immune regulation. Mechanistically, TIGIT on memory B cells controls immune response by directly acting on T cells and by arresting proinflammatory function of dendritic cells, resulting in the suppression of Th1, Th2, Th17, and CXCR5+ICOS+ T cell response while promoting immune regulatory function of T cells. TIGIT+ memory B cells are also superior to other B cells at expressing additional inhibitory molecules, including IL-10, TGFβ1, granzyme B, PD-L1, CD39/CD73, and TIM-1. Lack or decrease of TIGIT+ memory B cells is associated with increased donor-specific antibody and TFH response, and decreased Treg response in renal and liver allograft patients. Therefore, TIGIT+ human memory B cells play critical roles in immune regulation.

Background IL‐10‐producing regulatory B cells (Bregs) are widely ascribed immune regulatory functions. However, Breg subsets in human asthma have not been fully investigated. Objective We studied Breg subsets in adult allergic asthma patients by assessing two major parameters, frequency and IL‐10 expression. We then investigated factors that affect these two parameters in patients. Methods Peripheral blood mononuclear cells (PBMCs) of adult allergic asthma patients (N = 26) and non‐asthmatic controls (N = 28) were used to assess the frequency of five subsets of transitional B cells (TBs), three subsets of CD24highCD27+ B cells and B1 cells. In addition to clinical data, IL‐10 expression by individual Breg subsets was assessed by flow cytometry. Results Asthma patients had decreases of CD5+ and CD1d+CD5+, but an increase of CD27+ TBs which was significant in patients with moderate asthma (60 < FEV1 < 80). Regardless of asthma severity, there was no significant alteration in the frequencies of 6 other Breg subsets tested. However, we found that oral corticosteroid (OCS) significantly affected the frequency of Bregs in Breg subset‐specific manners. OCS decreased CD5+ and CD1d+CD5+ TBs, but increased CD27+ TBs and CD10+CD24highCD27+ cells. Furthermore, OCS decreased IL‐10 expression by CD27+ TBs, all 3 CD24highCD27+ B cell subsets (CD5+, CD10+ and CD1d+) and B1 cells. OCS‐mediated inhibition of IL‐10 expression was not observed in the other Breg subsets tested. Conclusion & Clinical Relevance Alterations in the frequency of Bregs and their ability to express IL‐10 are Breg subset‐specific. OCS treatment significantly affects the frequency as well as their ability to express IL‐10 in Breg subset‐specific manners.