期刊
NATURE
卷 591, 期 7850, 页码 458-+出版社
NATURE RESEARCH
DOI: 10.1038/s41586-021-03187-x
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资金
- National Institutes of Health (NIH) [5R37 AI037526]
- NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVID) [1UM1AI144462-01]
The germinal centre is a dynamic microenvironment where B cells expressing high-affinity antibody variants are selected for clonal expansion by limiting the number of T follicular helper cells. T follicular helper cells undergo antigen-dependent selection throughout the germinal centre reaction, resulting in differential proliferative expansion and contraction. Competition between T follicular helper cell clones is mediated by the affinity of T cell receptors for peptide-major-histocompatibility-complex ligands.
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.
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