Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity

Immunity. 2011 Jun 24;34(6):961-72. doi: 10.1016/j.immuni.2011.03.025.

Abstract

The transcription factor Bcl6 is essential for the development of germinal center (GC) B cells and follicular helper T (Tfh) cells. However, little is known about in vivo dynamics of Bcl6 protein expression during and after development of these cells. By using a Bcl6 reporter mouse strain, we found that antigen-engaged B cells upregulated Bcl6 before clustering in GCs. Two-photon microscopic analysis indicated that Bcl6 upregulation in pre-GC B cells contributed to sustaining their interactions with helper T cells and was required for their entry to GC clusters. Our data also suggested that Tfh cells gradually downmodulated Bcl6 protein over weeks after development. The Bcl6-low Tfh cells rapidly terminated proliferation and upregulated IL-7 receptor. These results clarify the role of Bcl6 in pre-GC B cell dynamics and highlight the modulation of Bcl6 expression in Tfh cells that persist in the late phase of the antibody response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • B-Lymphocytes / immunology*
  • Cell Proliferation
  • DNA-Binding Proteins / immunology*
  • Germinal Center / immunology*
  • Kinetics
  • Mice
  • Phenotype
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, Interleukin-7 / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Up-Regulation

Substances

  • Antigens
  • Bcl6 protein, mouse
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, Interleukin-7