Wichmann Christopher, Wirthgen Elisa, Nowosad Carla R, Däbritz Jan
Department of Paediatrics, Greifswald University Medical Centre, Ferdinand-Sauerbruch-Str.1, Greifswald, MV, 17457, Germany.
The David Rockefeller Graduate Program in Bioscience, The Rockefeller University, New York, NY, USA.
Mol Cell Pediatr. 2024 Aug 16;11(1):7. doi: 10.1186/s40348-024-00180-y.
The gut is an environment in which the immune system closely interacts with a vast number of foreign antigens, both inert such as food and alive, from the viral, bacterial, fungal and protozoal microbiota. Within this environment, germinal centres, which are microanatomical structures where B cells affinity-mature, are chronically present and active.
The functional mechanism by which gut-associated germinal centres contribute to gut homeostasis is not well understood. Additionally, the role of T cells in class switching to immunoglobulin A and the importance of B cell affinity maturation in homeostasis remains elusive. Here, we provide a brief overview of the dynamics of gut-associated germinal centres, T cell dependency in Immunoglobulin A class switching, and the current state of research regarding the role of B cell selection in germinal centres in the gut under steady-state conditions in gnotobiotic mouse models and complex microbiota, as well as in response to immunization and microbial colonization. Furthermore, we briefly link those processes to immune system maturation and relevant diseases.
B cell response at mucosal surfaces consists of a delicate interplay of many dynamic factors, including the microbiota and continuous B cell influx. The rapid turnover within gut-associated germinal centres and potential influences of an early-life window of immune system imprinting complicate B cell dynamics in the gut.
肠道是免疫系统与大量外来抗原密切相互作用的环境,这些抗原包括食物等惰性物质以及来自病毒、细菌、真菌和原生动物微生物群的活的抗原。在这种环境中,生发中心这种B细胞亲和力成熟的微解剖结构长期存在且活跃。
肠道相关生发中心促进肠道稳态的功能机制尚不清楚。此外,T细胞在向免疫球蛋白A类别转换中的作用以及B细胞亲和力成熟在稳态中的重要性仍不明确。在这里,我们简要概述肠道相关生发中心的动态变化、免疫球蛋白A类别转换中的T细胞依赖性,以及在无菌小鼠模型和复杂微生物群的稳态条件下,以及在免疫和微生物定植反应中,关于生发中心B细胞选择作用的研究现状。此外,我们简要地将这些过程与免疫系统成熟和相关疾病联系起来。
黏膜表面的B细胞反应由许多动态因素的微妙相互作用组成,包括微生物群和持续的B细胞流入。肠道相关生发中心的快速更新以及免疫系统印记的早期窗口期的潜在影响使肠道中的B细胞动态变得复杂。