Bach2 Controls T Follicular Helper Cells by Direct Repression of Bcl-6

J Immunol. 2019 Apr 15;202(8):2229-2239. doi: 10.4049/jimmunol.1801400. Epub 2019 Mar 4.

Abstract

T follicular helper (Tfh) cells are a specialized T cell subset that regulates the long-lived production of highly specific Abs by B cells during the germinal center (GC) reaction. However, the transcriptional network sustaining the Tfh cell phenotype and function is still incompletely understood. In this study, we identify the transcription factor Bach2 as a central negative regulator of Tfh cells. Ectopic overexpression of Bach2 in murine Tfh cells resulted in a rapid loss of their phenotype and subsequent breakdown of the GC response. Low Bach2 expression levels are required to maintain high expression of the signature cytokine IL-21, the coinhibitory receptor TIGIT and the transcriptional repressor Bcl-6. In stark contrast to the regulatory network in GC B cells, Bach2 in Tfh cells is not coexpressed with Bcl-6 at high levels to inhibit the antagonizing factor Blimp-1, but suppresses Bcl-6 by direct binding to the promoter. These data reveal that by replacing an activating complex of Batf and Irf-4 at the Bcl-6 promoter, Bach2 regulates the transcriptional network of Tfh cells in a different way, as in GC B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors* / genetics
  • Basic-Leucine Zipper Transcription Factors* / immunology
  • Gene Expression Regulation / immunology*
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology
  • Interleukins / genetics
  • Interleukins / immunology
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic / immunology
  • Proto-Oncogene Proteins c-bcl-6* / genetics
  • Proto-Oncogene Proteins c-bcl-6* / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Transcription, Genetic / immunology*

Substances

  • Bach2 protein, mouse
  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • Bcl6 protein, mouse
  • Interferon Regulatory Factors
  • Interleukins
  • Proto-Oncogene Proteins c-bcl-6
  • interferon regulatory factor-4
  • interleukin-21