T FH cells progressively differentiate to regulate the germinal center response

Jason S. Weinstein, Edward I. Herman, Begoña Lainez, Paula Licona-Limón, Enric Esplugues, Richard Flavell, Joe Craft

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1197-1205
Number of pages9
JournalNature Immunology
Issue number10
StatePublished - Sep 20 2016

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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