Bcl6 promotes follicular helper T-cell differentiation and PD-1 expression in a Blimp1-independent manner in mice

Markus M. Xie, Byung Hee Koh, Kristin Hollister, Hao Wu, Jie Sun, Mark H. Kaplan, Alexander L. Dent

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The transcription factors Bcl6 and Blimp1 have opposing roles in the development of the follicular helper T (TFH) cells: Bcl6 promotes and Blimp1 inhibits TFH-cell differentiation. Similarly, Bcl6 activates, while Blimp1 represses, expression of the TFH-cell marker PD-1. However, Bcl6 and Blimp1 repress each other's expression, complicating the interpretation of the regulatory network. Here we sought to clarify the extent to which Bcl6 and Blimp1 independently control TFH-cell differentiation by generating mice with T-cell specific deletion of both Bcl6 and Blimp1 (double conditional KO [dcKO] mice). Our data indicate that Blimp1 does not control TFH-cell differentiation independently of Bcl6. However, a population of T follicular regulatory (TFR) cells developed independently of Bcl6 in dcKO mice. We have also analyzed regulation of IL-10 and PD-1, two genes controlled by both Bcl6 and Blimp1, and observed that Bcl6 regulates both genes independently of Blimp1. We found that Bcl6 positively regulates PD-1 expression by inhibiting the ability of T-bet/Tbx21 to repress Pdcd1 transcription. Our data provide a novel mechanism for positive control of gene expression by Bcl6, and illuminate how Bcl6 and Blimp1 control TFH-cell differentiation.

Original languageEnglish (US)
Pages (from-to)1136-1141
Number of pages6
JournalEuropean Journal of Immunology
Volume47
Issue number7
DOIs
StatePublished - Jul 2017

Keywords

  • Bcl6
  • Blimp1
  • Follicular helper T cells
  • Germinal center
  • PD-1
  • T follicular regulatory cells
  • T-bet

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Bcl6 promotes follicular helper T-cell differentiation and PD-1 expression in a Blimp1-independent manner in mice'. Together they form a unique fingerprint.

  • Cite this