Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell retention in germinal centers

J Exp Med. 2014 Jun 30;211(7):1297-305. doi: 10.1084/jem.20131666. Epub 2014 Jun 9.

Abstract

Follicular helper T (Tfh) cells access the B cell follicle to promote antibody responses and are particularly important for germinal center (GC) reactions. However, the molecular mechanisms of how Tfh cells are physically associated with GCs are incompletely understood. We report that the sphingosine-1-phosphate receptor 2 (S1PR2) gene is highly expressed in a subpopulation of Tfh cells that localizes in GCs. S1PR2-deficient Tfh cells exhibited reduced accumulation in GCs due to their impaired retention. T cells deficient in both S1PR2 and CXCR5 were ineffective in supporting GC responses compared with T cells deficient only in CXCR5. These results suggest that S1PR2 and CXCR5 cooperatively regulate localization of Tfh cells in GCs to support GC responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Mice
  • Mice, Mutant Strains
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / immunology*
  • Receptors, Lysosphingolipid / genetics
  • Receptors, Lysosphingolipid / immunology*
  • Sphingosine-1-Phosphate Receptors
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • CXCR5 protein, mouse
  • Receptors, CXCR5
  • Receptors, Lysosphingolipid
  • Sphingosine-1-Phosphate Receptors
  • sphingosine-1-phosphate receptor-2, mouse

Associated data

  • GEO/GSE56883