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

ABSTRACT: Although viral infections elicit robust interferon-? (IFN-?) and long-lived antibody-secreting cell (ASC) responses, the roles for IFN-? and IFN-?-induced transcription factors (TFs) in ASC development are unclear. We showed that B cell intrinsic expression of IFN-?R and the IFN-?-induced TF T-bet were required for T-helper 1 cell-induced differentiation of B cells into ASCs. IFN-?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-?-activated B cells but instead regulated chromatin accessibility within the Ifng and Ifngr2 loci and repressed the IFN-?-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-?-activated inflammatory effector B cells into ASCs in the setting of IFN-?-, but not IL-4-, induced inflammatory responses.

SUBMITTER: Stone SL 

PROVIDER: S-EPMC6929688 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature