Bcl6 expression specifies the T follicular helper cell program in vivo

J Exp Med. 2012 Sep 24;209(10):1841-52, S1-24. doi: 10.1084/jem.20120219. Epub 2012 Sep 17.

Abstract

T follicular helper cells (Tfh cells) play a pivotal role in germinal center reactions, which require B cell lymphoma 6 (Bcl6) transcription factor. To analyze their relationships with other effector T cell lineages and their stability in vivo, we developed and analyzed a new Bcl6 reporter mouse alone or together with other lineage reporter systems. Assisted with genome-wide transcriptome analysis, we show substantial plasticity of T cell differentiation in the early phase of immune response. At this stage, CXCR5 appears to be expressed in a Bcl6-independent manner. Once Bcl6 is highly expressed, Tfh cells can persist in vivo and some of them develop into memory cells. Together, our results indicate Bcl6 as a bona fide marker for Tfh polarized program.

Publication types

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

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Cell Differentiation / immunology
  • Cluster Analysis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology
  • Gene Expression
  • Gene Expression Profiling
  • Gene Order
  • Gene Targeting
  • Genes, Reporter
  • Germinal Center / immunology
  • Immunologic Memory
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Transcription, Genetic

Substances

  • Bcl6 protein, mouse
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR5