CD19~+CD24~(hi)CD38~(hi) B Cells Maintain Regulatory T Cells While Limiting T_H1 and T_H17 Differentiation

摘要

The relevance of regulatory B cells in the maintenance of tolerance in healthy individuals or in patients with immune disorders remains understudied. In healthy individuals, CD19~+CD24~(hi)CD38~(hi) B cells suppress CD4~+CD25~? T cell proliferation as well as the release of interferon-γ and tumor necrosis factor–α by these cells; this suppression is partially mediated through the production of interleukin-10 (IL-10). We further elucidate the mechanisms of suppression by CD19~+CD24~(hi)CD38~(hi) B cells. Healthy CD19~+CD24~(hi)CD38~(hi) B cells inhibited na?ve T cell differentiation into T helper 1 (T_H1) and T_H17 cells and converted CD4~+CD25~? T cells into regulatory T cells (T_(regs)), in part through the production of IL-10. In contrast, CD19~+CD24~(hi)CD38~(hi) B cells from patients with rheumatoid arthritis (RA) failed to convert CD4~+CD25~? T cells into functionally suppressive T_(regs) or to curb T_H17 development; however, they maintained the capacity to inhibit T_H1 cell differentiation. Moreover, RA patients with active disease have reduced numbers of CD19~+CD24~(hi)CD38~(hi) B cells in peripheral blood compared with either patients with inactive disease or healthy individuals. These results suggest that in patients with active RA, CD19~+CD24~(hi)CD38~(hi) B cells with regulatory function may fail to prevent the development of autoreactive responses and inflammation, leading to autoimmunity.