B cells control lupus autoimmunity by inhibiting Th17 and promoting Th22 cells

B cells exert immunosuppressive effects and offer therapeutic potential for systemic lupus erythematosus (SLE), but the mechanism remains unclear. Here we analyzed the B cell regulation of Th17/Th22 cell differentiation in lupus and found that α-IgM- and α-CD40-activated B cells could inhibit Th17 and promote Th22 cell differentiation from naive T cells under Th17 cell culture conditions. B cell-induced Th22 cells demonstrated immunosuppressive effects and could decrease renal endothelial cell apoptosis in vitro. Moreover, activated B cell infusion relieved lupus injuries via IL-22 production in vivo. Mechanically, activated B cells affected Th17/Th22 cell differentiation by non-contact TNF-α secretion and mTOR activation. Finally, activated B cells could affect Th17/Th22 cell differentiation in human peripheral blood T cells. These data suggest that activated B cells might attenuate lupus autoimmunity by inhibiting Th17 but promoting Th22 cell differentiation, supporting B cell activation as a promising therapeutic for the treatment of lupus.