Regulatory roles for cytokine-producing B cells in infection and autoimmune disease.

Recent experiments have revealed that B cells can regulate the course of immune responses to pathogens and autoantigens by antibody-independent mechanisms. One antibody-independent function of B cells is to produce cytokines. In this review we describe the identification of IL-10-producing 'regulatory' B cells as well as IFNgamma-producing 'effector' Bel cells and IL-4-producing 'effector' Be2 cells. We discuss the roles of antigen, pathogen-derived molecules and T cell and dendritic cell-derived factors in regulating the differentiation of mature B cells into cytokine-producing effector B cells. We also review the recent experiments showing that B cell-derived cytokines play pathologic as well as protective roles in immune responses to autoantigens, and demonstrate that cytokine-producing B cells play unexpectedly complex and potentially opposing roles in autoimmune disease.