Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile

Nat Immunol. 2012 Mar 11;13(4):405-11. doi: 10.1038/ni.2242.


The transcription factors T-bet and Bcl-6 are required for the establishment of a T helper type 1 cell (T(H)1 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(H)1 cells. Mechanistically, the low concentrations of Bcl-6 normally found in effector T(H)1 cells did not repress its target genes because a T-bet-Bcl-6 complex masked the Bcl-6 DNA-binding domain. T(H)1 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(H)1 cells to maintain flexibility with a T(FH) cell-like gene profile.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology*
  • Immunoblotting
  • Immunoprecipitation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins c-bcl-6 / genetics*
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • Th1 Cells / cytology*
  • Th1 Cells / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcription Factors / metabolism
  • Transfection


  • Prdm1 protein, mouse
  • Proto-Oncogene Proteins c-bcl-6
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1