研究动态
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在人类淋巴结中,收敛进化与B细胞在生发中心的再循环。

Convergent evolution and B-cell recirculation in germinal centers in a human lymph node.

发表日期:2023 Nov
作者: Aurelien Pelissier, Maria Stratigopoulou, Naomi Donner, Evangelos Dimitriadis, Richard J Bende, Jeroen E Guikema, Maria Rodriguez Martinez, Carel Jm van Noesel
来源: Immunity & Ageing

摘要:

胚胎中心(GCs)在对传染性病原体产生有效免疫反应方面起着关键作用,其调节机制的失败可能导致自身免疫疾病和癌症的发展。尽管先前的研究使用小鼠模型对免疫反应的实验系统进行了研究,这些小鼠模型被免疫特定抗原,但我们的研究侧重于真实情况,即人体淋巴结(LN)中正在进行的GC反应,涉及多个异步的GC同时对未知抗原作出反应。我们将激光切割捕获技术与下一代测序相结合,对人体LN中的单个GC进行表征,将其视为独特的进化空间。与小鼠中的GC反应相一致,小鼠通过对模型抗原免疫引发的反应表明,同一个人体LN中的不同GC之间存在异质的克隆多样性。然而,我们在几个单个GC中发现了共享的克隆,并通过系统发育树分析和抗毒素模型显示出这些克隆在不同GC之间的重新参与和重新多样化,并且扩展的克隆在不同GC之间表现出共享的抗原反应,表明了GC的收敛演化。 © 2023 Pelissier et al.
Germinal centers (GCs) play a central role in generating an effective immune response against infectious pathogens, and failures in their regulating mechanisms can lead to the development of autoimmune diseases and cancer. Although previous works study experimental systems of the immune response with mouse models that are immunized with specific antigens, our study focused on a real-life situation, with an ongoing GC response in a human lymph node (LN) involving multiple asynchronized GCs reacting simultaneously to unknown antigens. We combined laser capture microdissection of individual GCs from human LN with next-generation repertoire sequencing to characterize individual GCs as distinct evolutionary spaces. In line with well-characterized GC responses in mice, elicited by immunization with model antigens, we observe a heterogeneous clonal diversity across individual GCs from the same human LN. Still, we identify shared clones in several individual GCs, and phylogenetic tree analysis combined with paratope modeling suggest the re-engagement and rediversification of B-cell clones across GCs and expanded clones exhibiting shared antigen responses across distinct GCs, indicating convergent evolution of the GCs.© 2023 Pelissier et al.