Reciprocal generation of Treg and Th1/Th17 cells by conventional B cells and B1 B cells (88.46)

Abstract Regulatory T cells (Treg) are indispensable for maintaining peripheral tolerance, whereas Th1 and Th17 cells induce inflammation and tissue destruction. Here we report a novel regulatory role for B cell subsets in influencing the differentiation of Treg versus Th1/Th17 cells. Using Foxp3-GFP knock-in mouse, we demonstrated that conventional B cells excelled in converting Foxp3− CD4 T cells into Foxp3+ Treg cells in the presence of IL-2 and TGFβ, whereas under the same conditions, peritoneal B1 cells preferentially generated Th1 and Th17 cells. We also demonstrated that B1 B cells promote stronger T cell proliferation during antigen presentation and MLR as compared to conventional B cells. Costimulation blockade of CD86 but not CD80 partially reversed the poor Treg conversion by B1 cells. Hence the ability to convert Treg is inversely correlated with B cell antigen-presentation capacity. Our findings suggest that different B cell subsets can play distinct roles in immune regulation by polarizing T cell functions. This study was supported by grants from the American Heart Association (0325807T), the Juvenile Diabetes Research Foundation (5-2006-19) and the National Institutes of Health (AI29690 and AI60896).