小柯机器人

美国洛克菲勒大学Julia Merkenschlager小组近日取得一项新成果。经过不懈努力，他们发现了生发中心反应过程中T_FH选择的动态调节机制。这一研究成果于2021年2月3日在线发表在国际学术期刊《自然》上。

研究人员揭示了生发中心反应过程中卵泡辅助性T细胞克隆的动态行为。研究发现，与生发中心B细胞相似，滤泡辅助性T细胞在整个生发中心反应中经历抗原依赖性选择，从而导致差异性增殖和收缩。生发中心抗原数量的增加导致滤泡辅助性T细胞的分裂增殖。滤泡辅助性T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物配体的亲和力所介导。

在生发中心优先扩增的T细胞具有T细胞受体下游基因表达增加的特点，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滤泡辅助性T细胞库的明显重塑。  。

据悉，生发中心是一个动态的微环境，在生发中心表达体细胞超突变产生高亲和力抗体的B细胞通过克隆扩增来限制卵泡辅助性T细胞的数量。尽管对于控制生发中心中B细胞选择的机制了解很多，但对调节这一过程滤泡辅助性T细胞的克隆行为却了解得很少。

附：英文原文

Title: Dynamic regulation of T FH selection during the germinal centre reaction

Author: 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, Michel C. Nussenzweig

Issue&Volume: 2021-02-03

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.

DOI: 10.1038/s41586-021-03187-x

Source: https://www.nature.com/articles/s41586-021-03187-x

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