Unique gene expression program of human germinal center T helper cells

Blood. 2004 Oct 1;104(7):1952-60. doi: 10.1182/blood-2004-03-1206. Epub 2004 Jun 22.

Abstract

Gene expression profiling was used to compare the gene expression patterns of human germinal center (GC) T helper (Th) cells with other CD4+ T-cell subsets (naive, central, and effector memory T cells). GC-Th cells, specifically localized in germinal centers to help B cells, are distantly related to central and effector memory T cells in global gene expression profiles. GC-Th cells displayed substantial differences in mRNA for adhesion molecules, chemoattractant receptors, and cytokines compared with other populations. Distinct expression of transcriptional factors by GC-Th cells is consistent with the hypothesis that they may be different from other T cells in cell lineage. Interestingly, CXCL13, a critical chemokine for B-cell entry to lymphoid follicles, is one of the most highly up-regulated genes in GC-Th cells. GC-Th cells (but not other T cells) produce and secrete large amounts of functional CXCL13 upon T-cell receptor activation, a process that is dependent on costimulation, requires translation and transcription, and is dramatically enhanced by activation in the presence of GC-B cells. This study revealed for the first time the unique gene expression program of GC-Th cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Chemokine CXCL13
  • Chemokines, CXC / biosynthesis
  • Chemotaxis
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Germinal Center / metabolism*
  • Humans
  • Immunohistochemistry
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Up-Regulation

Substances

  • CXCL13 protein, human
  • Chemokine CXCL13
  • Chemokines, CXC
  • RNA, Messenger