Cytokine-secreting follicular T cells shape the antibody repertoire

Nat Immunol. 2009 Apr;10(4):385-93. doi: 10.1038/ni.1715. Epub 2009 Mar 1.


High-affinity antibodies are critical for host protection and underlie successful vaccines. The generation of such antibodies requires T cell-dependent help, which mediates germinal center reactions in which mutation and selection of B cells occurs. Using an interleukin 4-reporter system, we show here that CD4(+) follicular helper T cells constituted essentially all of the cytokine-secreting T cells in lymph nodes and were functionally distinct from T cells secreting the same cytokine in peripheral tissues. Follicular helper T cells with different cytokine profiles could be isolated as conjugates with B cells undergoing cytokine-specific immunoglobulin class switching with evidence of somatic hypermutation. Our findings support a model in which B cells compete for cytokines produced by follicular helper T cells that shape the affinity and isotype of the antibody response.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / immunology*
  • Antibody Formation
  • Antigen Presentation / immunology
  • B-Lymphocytes / immunology
  • Genes, Reporter
  • Germinal Center / immunology*
  • Immunoglobulin Class Switching
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Leishmania major / immunology
  • Leishmaniasis, Cutaneous / immunology
  • Lymph Nodes / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Somatic Hypermutation, Immunoglobulin
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Antibodies
  • Interleukin-4