小柯机器人

美国洛克菲勒大学Gabriel D. Victora团队发现，克隆替代维持由呼吸道病毒激发的长期生发中心。2022年12月23日，《细胞》杂志在线发表了这项成果。

研究人员表示，生发中心（GC）在二级淋巴器官中形成，对感染和免疫有反应，是亲和力成熟的B细胞的来源。GC反应的持续时间跨度很大，长期GC（LLGC）有可能是高度突变的B细胞的来源。

研究人员表明，流感病毒或SARS-CoV-2感染引起的LLGC不是由不断演化的B细胞克隆组成的，而是由原始克隆逐渐被未检测到与病毒抗原结合的初始来源入侵者B细胞所取代而维持。罕见的、能长期抵抗替换的创始者克隆富含严重变异的免疫球蛋白，包括一些对抗原有非常高亲和力的克隆，这些克隆可以通过增殖而被召回。这些研究结果揭示了由呼吸道病毒感染产生的LLGC生物学中未被重视的方面，并确定了克隆替换是这些结构中高度突变抗体发展的一个潜在制约因素。

附：英文原文

Title: Clonal replacement sustains long-lived germinal centers primed by respiratory viruses

Author: Renan V.H. de Carvalho, Jonatan Ersching, Alexandru Barbulescu, Alvaro Hobbs, Tiago B.R. Castro, Luka Mesin, Johanne T. Jacobsen, Brooke K. Phillips, Hans-Heinrich Hoffmann, Roham Parsa, Maria Cecilia C. Canesso, Carla R. Nowosad, Allan Feng, Sarah R. Leist, Ralph S. Baric, Emily Yang, P.J. Utz, Gabriel D. Victora

Issue&Volume: 2022-12-23

Abstract: Germinal centers (GCs) form in secondary lymphoid organs in response to infectionand immunization and are the source of affinity-matured B cells. The duration of GCreactions spans a wide range, and long-lasting GCs (LLGCs) are potentially a sourceof highly mutated B cells. We show that rather than consisting of continuously evolvingB cell clones, LLGCs elicited by influenza virus or SARS-CoV-2 infection in mice aresustained by progressive replacement of founder clones by naive-derived invader Bcells that do not detectably bind viral antigens. Rare founder clones that resistreplacement for long periods are enriched in clones with heavily mutated immunoglobulins,including some with very high affinity for antigen, that can be recalled by boosting.Our findings reveal underappreciated aspects of the biology of LLGCs generated byrespiratory virus infection and identify clonal replacement as a potential constrainton the development of highly mutated antibodies within these structures.

DOI: 10.1016/j.cell.2022.11.031

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01506-9