Antigen sampling by intestinal M cells is the principal pathway initiating mucosal IgA production to commensal enteric bacteria.
Antigen sampling by intestinal M cells is the principal pathway initiating mucosal IgA production to commensal enteric bacteria.
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DOI：
10.1038/mi.2015.121
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发表时间：
2016-07
影响因子：
8
通讯作者：
Williams IR
中科院分区：
文献类型：
--
作者：
Rios D;Wood MB;Li J;Chassaing B;Gewirtz AT;Williams IR
针对肠道常驻细菌的分泌型 IgA (SIgA) 使哺乳动物粘膜免疫系统能够在断奶后与共生肠道微生物群建立稳态。派尔氏集结 (PP) 中的生发中心 (GC) 是主要的诱导位点，其中针对细菌抗原的幼稚 B 细胞遇到其同源抗原，并接受 T 细胞帮助驱动其分化为产生 IgA 的浆细胞。我们通过培养小鼠来研究肠道 M 细胞抗原采样在启动对肠道细菌的 SIgA 反应中的作用，在这些小鼠中，通过条件性删除肠上皮中的 Tnfrsf11a，消除了核因子 κB 配体 (RANKL) 依赖性 M 细胞分化的受体激活剂。没有肠道 M 细胞的小鼠 PP GC 成熟和固有层 IgA 浆细胞的出现严重延迟，导致粪便 SIgA 水平下降，并持续到成年期。我们得出的结论是，M 细胞介导的共生细菌取样是有效诱导肠道 SIgA 所需的初始步骤。
Secretory IgA (SIgA) directed against gut resident bacteria enables the mammalian mucosal immune system to establish homeostasis with the commensal gut microbiota after weaning. Germinal centers (GCs) in Peyer's patches (PPs) are the principal inductive sites where naive B cells specific for bacterial antigens encounter their cognate antigens and receive T-cell help driving their differentiation into IgA-producing plasma cells. We investigated the role of antigen sampling by intestinal M cells in initiating the SIgA response to gut bacteria by developing mice in which receptor activator of nuclear factor-κB ligand (RANKL)-dependent M-cell differentiation was abrogated by conditional deletion of Tnfrsf11a in the intestinal epithelium. Mice without intestinal M cells had profound delays in PP GC maturation and emergence of lamina propria IgA plasma cells, resulting in diminished levels of fecal SIgA that persisted into adulthood. We conclude that M-cell-mediated sampling of commensal bacteria is a required initial step for the efficient induction of intestinal SIgA.