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

Academic Article

Abstract

  • © 2019 Elsevier Inc. Although viral infections elicit robust interferon-γ (IFN-γ)and long-lived antibody-secreting cell (ASC)responses, the roles for IFN-γ and IFN-γ-induced transcription factors (TFs)in ASC development are unclear. We showed that B cell intrinsic expression of IFN-γR and the IFN-γ-induced TF T-bet were required for T-helper 1 cell-induced differentiation of B cells into ASCs. IFN-γR 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-γ-activated B cells but instead regulated chromatin accessibility within the Ifng and Ifngr2 loci and repressed the IFN-γ-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-γ-activated inflammatory effector B cells into ASCs in the setting of IFN-γ-, but not IL-4-, induced inflammatory responses.
  • Digital Object Identifier (doi)

    Author List

  • Stone SL; Peel JN; Scharer CD; Risley CA; Chisolm DA; Schultz MD; Yu B; Ballesteros-Tato A; Wojciechowski W; Mousseau B
  • Start Page

  • 1172
  • End Page

  • 1187.e7
  • Volume

  • 50
  • Issue

  • 5