Dynamic regulation of TFH selection during the germinal centre reaction

Julia Merkenschlager (), Shlomo Finkin, Victor Ramos, Julian Kraft, Melissa Cipolla, Carla R. Nowosad, Harald Hartweger, Wenzhu Zhang, Paul Dominic B. Olinares, Anna Gazumyan, Thiago Y. Oliveira, Brian T. Chait and Michel C. Nussenzweig
Additional contact information
Julia Merkenschlager: The Rockefeller University
Shlomo Finkin: The Rockefeller University
Victor Ramos: The Rockefeller University
Julian Kraft: The Rockefeller University
Melissa Cipolla: The Rockefeller University
Carla R. Nowosad: The Rockefeller University
Harald Hartweger: The Rockefeller University
Wenzhu Zhang: The Rockefeller University
Paul Dominic B. Olinares: The Rockefeller University
Anna Gazumyan: The Rockefeller University
Thiago Y. Oliveira: The Rockefeller University
Brian T. Chait: The Rockefeller University
Michel C. Nussenzweig: The Rockefeller University

Nature, 2021, vol. 591, issue 7850, 458-463

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-021-03187-x

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