Dynamic regulation of T FH selection during the germinal centre reaction.

Autor: Merkenschlager J; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA. jmerkensch@rockefeller.edu., Finkin S; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA., Ramos V; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA., Kraft J; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA., Cipolla M; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA., Nowosad CR; Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA., Hartweger H; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA., Zhang W; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY, USA., Olinares PDB; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY, USA., Gazumyan A; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.; Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA., Oliveira TY; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA., Chait BT; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY, USA., Nussenzweig MC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.; Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Mar; Vol. 591 (7850), pp. 458-463. Date of Electronic Publication: 2021 Feb 03.
DOI: 10.1038/s41586-021-03187-x
Abstrakt: 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 cells 1,2 . 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.
Databáze: MEDLINE
Externí odkaz: