Several Follicular Regulatory T Cell Subsets With Distinct Phenotype and Function Emerge During Germinal Center Reactions

Front Immunol. 2018 Aug 13;9:1792. doi: 10.3389/fimmu.2018.01792. eCollection 2018.


An efficient B cell immunity requires a dynamic equilibrium between positive and negative signals. In germinal centers (GCs), T follicular helper cells are supposed to be the positive regulator while T follicular regulatory (Tfr) cells were assigned to be the negative regulators. Indeed, Tfr cells are considered as a homogenous cell population dedicated to dampen the GC extent. Moreover, Tfr cells prevent autoimmunity since their dysregulation leads to production of self-reactive antibodies (Ab). However, a growing corpus of evidence has revealed additional and unexpected functions for Tfr cells in the regulation of B cell responses. This review provides an overview of the Tfr cell contribution and presents Tfr cell proprieties in the context of vaccination.

Keywords: T follicular helper cells; T follicular regulatory cells; germinal centers; heterogeneity; subsets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens / immunology
  • Cell Differentiation
  • Epitopes, T-Lymphocyte / immunology
  • Gene Expression Regulation
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Germinal Center / metabolism*
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immune System / cytology
  • Immune System / immunology
  • Immune System / metabolism
  • Immunomodulation
  • Phenotype*
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*


  • Antigens
  • Epitopes, T-Lymphocyte