Bacterially activated B-cells drive T cell differentiation towards Tr1 through PD-1/PD-L1 expression


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Abstract

Regulatory B cells (Bregs) play a crucial role in immunological tolerance primarily through the production of IL-10 in many diseases including autoimmune disorders, allergy, infectious diseases, and cancer. To date, various Breg subsets with overlapping phenotypes have been identified. However, the roles of Bregs in Helicobacter infection are largely unknown. In the present study, we investigate the phenotype and function of Helicobacter −stimulated B cells. Our results demonstrate that Helicobacter felis −stimulated IL-10- producing B cells (Hfstim- IL-10+ B) are composed of B10 and Transitional 2 Marginal Zone Precursor (T2-MZP) cells with expression of CD9, Tim-1, and programmed death 1 (PD-1). On the other hand, Helicobacter felis −stimulated IL-10- nonproducing B (Hfstim- IL-10 B) cells are mainly marginal zone (MZ) B cells that express PD-L1 and secrete TGF-β, IL-6, and TNF-α, and IgM and IgG2b. Furthermore, we show that both Hfstim- IL-10+ B cells and Hfstim- IL-10 B cells induce CD49b+LAG-3+ Tr1 cells. Here, we describe a novel mechanism for PD-1/PD-L1- driven B cell-dependent Tr1 cell differentiation. Finally, we explore the capability of Hfstim- IL-10 B cells to induce Th17 cell differentiation, which we find to be dependent on TGF-β. Taken together, the current study demonstrates that Hfstim- B cells induce Tr1 cells through the PD-1/PD-L1 axis and Th17 cells by secreting TGF-β.HighlightsHfstim- IL-10+ and IL-10 B cells are composed of B10 and T2-MZP, and MZ B cells, respectively.Hfstim- IL-10+ B cells express CD9, Tim-1, and PD-1, whereas Hfstim- IL-10 B cells express PD-L1 on their surface.Hfstim- IL-10 B cells produce TGF-β, IL-6, and TNF-α cytokines, and secretes IgM and IgG2b antibodies.Hfstim-B cell-driven Tr1 cell differentiation is dependent on PD-1/PD-L1 expression.Hfstim- IL-10 B cells induce Th17 cell differentiation through the secretion of TGF-β.

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