Molecular mechanisms that control the expression and activity of Bcl-6 in T H1 cells to regulate flexibility with a T FH-like gene profile

Academic Article

Abstract

  • The transcription factors T-bet and Bcl-6 are required for the establishment of a T helper type 1 cell (T H1 cell) and follicular helper T cell (T FH cell) gene-expression profile, respectively. Here we found that high concentrations of interleukin 2 (IL-2) inhibited Bcl-6 expression in polarized T H1 cells. Mechanistically, the low concentrations of Bcl-6 normally found in effector T H1 cells did not repress its target genes because a T-bet-Bcl-6 complex masked the Bcl-6 DNA-binding domain. T H1 cells increased their Bcl-6/T-bet ratio in response to limiting IL-2 conditions, which allowed excess Bcl-6 to repress its direct target Prdm1 (which encodes the transcriptional repressor Blimp-1). The Bcl-6-dependent repression of Blimp-1 effectively induced a partial T FH profile because Blimp-1 directly repressed a subset of T FH signature genes, including Cxcr5. Thus, IL-2-signaling regulates the Bcl-6-Blimp-1 axis in T H1 cells to maintain flexibility with a T FH cell-like gene profile. © 2012 Nature America, Inc. All rights reserved.
  • Published In

  • Nature Immunology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Oestreich KJ; Mohn SE; Weinmann AS
  • Start Page

  • 405
  • End Page

  • 411
  • Volume

  • 13
  • Issue

  • 4