TFH cells progressively differentiate to regulate the germinal center response

Nat Immunol. 2016 Oct;17(10):1197-1205. doi: 10.1038/ni.3554. Epub 2016 Aug 29.


Germinal center (GC) B cells undergo affinity selection, which depends on interactions with CD4(+) follicular helper T cells (TFH cells). We found that TFH cells progressed through transcriptionally and functionally distinct stages and provided differential signals for GC regulation. They initially localized proximally to mutating B cells, secreted interleukin 21 (IL-21), induced expression of the transcription factor Bcl-6 and selected high-affinity B cell clones. As the GC response evolved, TFH cells extinguished IL-21 production and switched to IL-4 production, showed robust expression of the co-stimulatory molecule CD40L, and promoted the development of antibody-secreting B cells via upregulation of the transcription factor Blimp-1. Thus, TFH cells in the B cell follicle progressively differentiate through stages of localization, cytokine production and surface ligand expression to 'fine tune' the GC reaction.

MeSH terms

  • Animals
  • Antibody Affinity
  • B-Lymphocytes / immunology*
  • CD4 Antigens / metabolism
  • Cell Communication
  • Cell Differentiation
  • Cells, Cultured
  • Gene Expression Regulation
  • Germinal Center / immunology*
  • Humans
  • Interleukin-4 / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutation / genetics
  • Nippostrongylus / immunology*
  • Positive Regulatory Domain I-Binding Factor 1
  • Strongylida Infections
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • CD4 Antigens
  • Interleukins
  • Prdm1 protein, mouse
  • Transcription Factors
  • Interleukin-4
  • Positive Regulatory Domain I-Binding Factor 1
  • interleukin-21