Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

Abstract

Regulatory T (T(reg)) cells are indispensable for maintaining peripheral tolerance, whereas T helper (Th)1 and Th17 cells induce inflammation and tissue destruction. Using Foxp3-GFP knock-in mice, we report a novel regulatory role for B cell subsets in influencing the differentiation of T(reg) versus Th1/Th17 cells. Peritoneal B1 cells strongly promoted T cell proliferation and cytokine secretion when presenting nominal or allogeneic antigens, as compared to conventional follicular B (B2) cells. However, peritoneal B1 cells largely failed to convert naive Foxp3(-)CD4(+) T cells into Foxp3(+) T(reg) cells in the presence of TGF-beta and IL-2, in marked contrast to conventional B2 cells, which excelled in T(reg) conversion. Interestingly, under the same T(reg) conversion conditions, peritoneal B1 cells preferentially promoted Th1 and Th17 cell differentiation. Blockade of CD86 but not CD80 costimulation markedly enhanced T(reg) cell induction by B1 cells. Thus, B cell antigen presentation function is inversely correlated with de novo T(reg) cell induction for these B cell subsets. Our findings suggest that B1 and B2 cell subsets play distinct roles in immune regulation by promoting reciprocal differentiation of T cell lineages.