T-bet Transcription Factor Promotes Antibody-Secreting Cell Differentiation by Limiting the Inflammatory Effects of IFN-γ on B Cells

Although viral infections elicit robust interferon-gamma (IFN-gamma) and long-lived antibody-secreting cell (ASC) responses, the roles for IFN-gamma and IFN-gamma-induced transcription factors (TFs) in ASC development are unclear. We showed that B cell intrinsic expression of IFN-gamma R and the IFN-gamma-induced TF T-bet were required for T-helper 1 cell-induced differentiation of B cells into ASCs. IFN-gamma R signaling induced Blimp1 expression in B cells but also initiated an inflammatory gene program that, if not restrained, prevented ASC formation. T-bet did not affect Blimp1 upregulation in IFN-gamma-activated B cells but instead regulated chromatin accessibility within the Ifng and Ifngr2 loci and repressed the IFN-gamma-induced inflammatory gene program. Consistent with this, B cell intrinsic T-bet was required for formation of long-lived ASCs and secondary ASCs following viral, but not nematode, infection. Therefore, T-bet facilitates differentiation of IFN-gamma-activated inflammatory effector B cells into ASCs in the setting of IFN-gamma-, but not IL-4-, induced inflammatory responses.