In vivo regulation of Bcl6 and T follicular helper cell development

J Immunol. 2010 Jul 1;185(1):313-26. doi: 10.4049/jimmunol.0904023. Epub 2010 Jun 2.

Abstract

Follicular helper T (T(FH)) cells, defined by expression of the surface markers CXCR5 and programmed death receptor-1 (PD-1) and synthesis of IL-21, require upregulation of the transcriptional repressor Bcl6 for their development and function in B cell maturation in germinal centers. We have explored the role of B cells and the cytokines IL-6 and IL-21 in the in vivo regulation of Bcl6 expression and T(FH) cell development. We found that T(FH) cells are characterized by a Bcl6-dependent downregulation of P-selectin glycoprotein ligand 1 (PSGL1, a CCL19- and CCL21-binding protein), indicating that, like CXCR5 and PD-1 upregulation, modulation of PSGL1 expression is part of the T(FH) cell program of differentiation. B cells were neither required for initial upregulation of Bcl6 nor PSGL1 downregulation, suggesting these events preceded T-B cell interactions, although they were required for full development of the T(FH) cell phenotype, including CXCR5 and PD-1 upregulation, and IL-21 synthesis. Bcl6 upregulation and T(FH) cell differentiation were independent of IL-6 and IL-21, revealing that either cytokine is not absolutely required for development of Bcl6(+) T(FH) cells in vivo. These data increase our understanding of Bcl6 regulation in T(FH) cells and their differentiation in vivo and identifies a new surface marker that may be functionally relevant in this subset.

Publication types

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

MeSH terms

  • Animals
  • Cell Communication / immunology
  • Cell Differentiation / immunology*
  • Cricetinae
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Down-Regulation / immunology
  • Female
  • Immunophenotyping
  • Lymphocyte Cooperation / immunology
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-6
  • Spleen / cytology
  • Spleen / immunology*
  • Spleen / 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*
  • Up-Regulation / immunology

Substances

  • Bcl6 protein, mouse
  • DNA-Binding Proteins
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Proto-Oncogene Proteins c-bcl-6

Associated data

  • GEO/GSE20735