Expression of Foxp3 by T follicular helper cells in end-stage germinal centers

Science. 2021 Jul 16;373(6552):eabe5146. doi: 10.1126/science.abe5146. Epub 2021 Jul 15.


Germinal centers (GCs) are the site of immunoglobulin somatic hypermutation and affinity maturation, processes essential to an effective antibody response. The formation of GCs has been studied in detail, but less is known about what leads to their regression and eventual termination, factors that ultimately limit the extent to which antibodies mature within a single reaction. We show that contraction of immunization-induced GCs is immediately preceded by an acute surge in GC-resident Foxp3+ T cells, attributed at least partly to up-regulation of the transcription factor Foxp3 by T follicular helper (TFH) cells. Ectopic expression of Foxp3 in TFH cells is sufficient to decrease GC size, implicating the natural up-regulation of Foxp3 by TFH cells as a potential regulator of GC lifetimes.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / physiology
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Genes, T-Cell Receptor
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Immunization
  • Immunophenotyping
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Single-Cell Analysis
  • T Follicular Helper Cells / immunology
  • T Follicular Helper Cells / metabolism*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / physiology
  • Up-Regulation


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse