Bcl6 mediates the development of T follicular helper cells

Science. 2009 Aug 21;325(5943):1001-5. doi: 10.1126/science.1176676. Epub 2009 Jul 23.

Abstract

A fundamental function of CD4+ helper T (T(H)) cells is the regulation of B cell-mediated humoral immunity. Development of T follicular helper (T(FH)) cells that provide help to B cells is mediated by the cytokines interleukin-6 and interleukin-21 but is independent of TH1, TH2, and TH17 effector cell lineages. Here, we characterize the function of Bcl6, a transcription factor selectively expressed in T(FH) cells. Bcl6 expression is regulated by interleukin-6 and interleukin-21. Bcl6 overexpression induced T(FH)-related gene expression and inhibited other T(H) lineage cell differentiation in a DNA binding-dependent manner. Moreover, Bcl6 deficiency in T cells resulted in impaired T(FH) cell development and germinal center reactions, and altered production of other effector T cell subsets. Our data thus illustrate that Bcl6 is required for programming of T(FH) cell generation.

Publication types

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

MeSH terms

  • Animals
  • Antibody Formation
  • B-Lymphocytes / immunology
  • Cell Differentiation
  • Cell Lineage
  • Cytokines / immunology
  • Cytokines / metabolism
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Immunoglobulins / biosynthesis
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Interleukins / immunology
  • Interleukins / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Bcl6 protein, mouse
  • Cytokines
  • DNA-Binding Proteins
  • Immunoglobulins
  • Interleukin-6
  • Interleukins
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger
  • Transcription Factors
  • interleukin-21