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生发中心反应期间 T 细胞选择的动态调控。

Dynamic regulation of T selection during the germinal centre reaction.

机构信息

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.

Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.

出版信息

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

DOI:10.1038/s41586-021-03187-x
PMID:33536617
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7979475/
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 cells. 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.

摘要

生发中心是一个动态的微环境，其中表达高亲和力抗体变体的 B 细胞通过体细胞超突变被选择进行克隆扩增，方法是限制滤泡辅助性 T 细胞（Tfh）的数量。尽管人们对控制生发中心 B 细胞选择的机制了解很多，但对有助于调节这一过程的 Tfh 的克隆行为却知之甚少。在这里，我们报告了生发中心反应过程中 Tfh 克隆的动态行为。我们发现，与生发中心 B 细胞类似，Tfh 细胞在整个生发中心反应过程中经历抗原依赖性选择，导致增殖和收缩的差异。生发中心内呈现的抗原量增加会导致 Tfh 细胞的分裂增加。Tfh 克隆之间的竞争是由 T 细胞受体对肽-MHC 配体的亲和力介导的。在生发中心优先扩增的 T 细胞表现出 T 细胞受体下游基因的表达增加，例如代谢重编程、细胞分裂和细胞因子产生所需的基因。这些动态变化导致生发中心反应过程中功能性 Tfh 细胞库的显著重塑。

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