Dynamic regulation of TFH selection during the germinal centre reaction

Nature. 2021 Mar;591(7850):458-463. doi: 10.1038/s41586-021-03187-x. Epub 2021 Feb 3.

Abstract

The germinal centre is a dynamic microenvironment in which B cells that express high-affinity antibody variants produced by somatic hypermutation are selected for clonal expansion by limiting the numbers of T follicular helper cells1,2. Although much is known about the mechanisms that control the selection of B cells in the germinal centre, far less is understood about the clonal behaviour of the T follicular helper cells that help to regulate this process. Here we report on the dynamic behaviour of T follicular helper cell clones during the germinal centre reaction. We find that, similar to germinal centre B cells, T follicular helper cells undergo antigen-dependent selection throughout the germinal centre reaction that results in differential proliferative expansion and contraction. Increasing the amount of antigen presented in the germinal centre leads to increased division of T follicular helper cells. Competition between T follicular helper cell clones is mediated by the affinity of T cell receptors for peptide-major-histocompatibility-complex ligands. T cells that preferentially expand in the germinal centre show increased expression of genes downstream of the T cell receptor, such as those required for metabolic reprogramming, cell division and cytokine production. These dynamic changes lead to marked remodelling of the functional T follicular helper cell repertoire during the germinal centre reaction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Proliferation
  • Clone Cells / cytology
  • Clone Cells / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Germinal Center / cytology*
  • Germinal Center / immunology*
  • Male
  • Mice
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction / immunology
  • T Follicular Helper Cells / cytology*
  • T Follicular Helper Cells / immunology*
  • T Follicular Helper Cells / metabolism

Substances

  • Cytokines
  • Receptors, Antigen, T-Cell