Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4 T cells and is independent of CD57 expression

Eur J Immunol. 2006 Jul;36(7):1892-903. doi: 10.1002/eji.200636136.


The generation of high-affinity antibody-secreting plasma cells critically depends on the presence of CD4 T cells during the germinal center (GC) reaction. GC T cells are so far incompletely characterized in terms of phenotype and function. Here, we show that human follicular B helper T (T(FH)) cells are characterized by high expression of the homeostatic chemokine receptor CXCR5 and the costimulatory molecule ICOS, but not CD57 expression. CXCR5(hi)ICOS(hi) CD4 T cells are the most potent inducers of IgG production that also secrete large amounts of the B cell-attracting chemokine CXCL13. CXCR5(hi)ICOS(hi) CD4 T cells differ from other tonsillar CD4 T cell subsets in their stimulatory activity, proliferative capacity and susceptibility to apoptosis. Large-scale gene expression analysis revealed that T(FH) cells are only distantly related to CXCR5(-) and CXCR5(+) central memory T (T(CM)) as well as effector memory T (T(EM)) cells present in the periphery. CXCR5(hi)ICOS(hi) CD4 T cells appear to be terminally differentiated T helper cells that express a unique set of transcription factors related to the Notch signaling pathway and thus differentiate independent of other T helper cell populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / biosynthesis*
  • Apoptosis / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD57 Antigens / biosynthesis*
  • CD57 Antigens / genetics
  • CD57 Antigens / physiology
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Humans
  • Inducible T-Cell Co-Stimulator Protein
  • Lymphocyte Cooperation / immunology
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology*
  • Palatine Tonsil / metabolism
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine / biosynthesis*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism


  • Antigens, Differentiation, T-Lymphocyte
  • CD57 Antigens
  • CXCR5 protein, human
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • Receptors, CXCR5
  • Receptors, Chemokine
  • Receptors, Cytokine