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Dynamic regulation of TFH selection during the germinal centre reaction

机译：发芽中心反应过程中TFH选择的动态调节

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摘要

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.
机译：发芽中心是一种动态微环境，其中通过限制T滤泡辅助细胞（1,2）的数量来选择表达通过体细胞增强的高亲和力抗体变体的B细胞进行克隆膨胀。虽然关于控制发芽中心中B细胞的选择的机制非常了解，但是据了解有助于调节该过程的T滤泡辅助细胞的克隆行为远远较低。在这里，我们报道了发芽中心反应过程中T滤泡辅助细胞克隆的动态行为。我们发现，类似于发芽中心B细胞，T滤泡辅助细胞在整个生发中心反应中经历抗原依赖性选择，导致差异增殖性膨胀和收缩。增加生发中心中呈现的抗原的量导致T卵泡辅助细胞的逐分。 T卵泡辅助细胞克隆之间的竞争是由T细胞受体对肽 - 主要组织相容性 - 复合配体的亲和力的介导的。优先在发芽中心膨胀的T细胞显示T细胞受体下游的基因表达增加，例如代谢重编程，细胞分裂和细胞因子产生所需的基因。这些动态变化导致在发芽中心反应过程中标记功能性T滤泡助手细胞曲目的重塑。

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  • 来源
    《Nature》 |2021年第7850期|458-463|共6页
  • 作者

    Merkenschlager Julia; Finkin Shlomo; Ramos Victor; Kraft Julian; Cipolla Melissa; Nowosad Carla R.; Hartweger Harald; Zhang Wenzhu; Olinares Paul Dominic B.; Gazumyan Anna; Oliveira Thiago Y.; Chait Brian T.; Nussenzweig Michel C.;

  • 作者单位

    Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Lymphocyte Dynam 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mass Spectrometry & Gaseous Ion Chem 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mass Spectrometry & Gaseous Ion Chem 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA|Rockefeller Univ Howard Hughes Med Inst 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mass Spectrometry & Gaseous Ion Chem 1230 York Ave New York NY 10021 USA;

    Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA|Rockefeller Univ Howard Hughes Med Inst 1230 York Ave New York NY 10021 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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