Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice

B cells can serve dual roles in modulating T cell immunity through their po tent capacity to present Ag and induce regulatory tolerance. Although B cel ls are necessary components for the initiation of spontaneous T cell autoim munity to beta cell Ags in nonobese diabetic (NOD) mice, the role of activa ted B cells in the autoimmune process is poorly understood. In this study, we show that LPS-activated B cells, but not control B cells, express Fas li gand and secrete TGF-beta. Coincubation of diabetogenic T cells with activa ted B cells in vitro leads to the apoptosis of both T and B lymphocytes. Tr ansfusion of activated B cells, but not control B cells, into prediabetic N OD mice inhibited spontaneous Th1 autoimmunity, but did not promote Th2 res ponses to beta cell autoantigens. Furthermore, this treatment induced monon uclear cell apoptosis predominantly in the spleen and temporarily impaired the activity of APCs. Cotransfer of activated B cells with diabetogenic spl enic T cells prevented the adoptive transfer of type I diabetes mellitus (T 1DM) to NOD/scid mice. Importantly, whereas 90% of NOD mice treated with co ntrol B cells developed T1DM within 27 wk, < 20% of the NOD mice treated wi th activated B cells became hyperglycemic up to 1 year of age. Our data sug gest that activated B cells can down-regulate pathogenic Th1 immunity throu gh triggering the apoptosis of Th1 cells and/or inhibition of APC activity by the secretion of TGF-beta. These findings provide new insights into T-B cell interactions and may aid in the design of new therapies for human T1DM .