1月12日,,國際著名雜志Nature在線刊登了加拿大多倫多大學研究人員的最新研究成果“Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut”,,文章中,,作者通過研究揭示了腸道淋巴細胞的重要作用。
淋巴細胞是白細胞的一種,。由淋巴器官產生,,機體免疫應答功能的重要細胞成分。淋巴器官根據(jù)其發(fā)生和功能的差異,,可分為中樞淋巴器官和周圍淋巴器官兩類,。前者包括胸腺、腔上囊或其相當器官(有人認為在哺乳動物是骨髓),。它們無須抗原刺激即可不斷增殖淋巴細胞,,成熟后將其轉送至周圍淋巴器官。后者包括脾,、淋巴結等,。成熟淋巴細胞需依賴抗原刺激而分化增殖,繼而發(fā)揮其免疫功能,。
腸道含有大量對生物體健康來說所必需的細菌,,但也是淋巴細胞的一個豐富來源,后者的存在是為了消除感染,。淋巴細胞怎樣不讓自己去攻擊有益菌,、同時又能夠對真正的病原體做出反應?Fritz等人發(fā)現(xiàn),,在B-細胞分化成腸道中的漿細胞時,,它們采取一種與先天免疫細胞相似的表現(xiàn)型(炎性單核細胞),同時保持自己生成免疫球蛋白的能力,。這樣在固有層中所產生的“免疫球蛋白-A分泌漿細胞”,,被發(fā)現(xiàn)是在小腸細菌和免疫系統(tǒng)之間維持平衡所需的抗菌調控物質“腫瘤壞死因子-α”和“可誘導性一氧化氮合成酶”的一個主要來源。(生物谷Bioon.com)
doi:10.1038/nature10698
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Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut
Jörg H. Fritz, Olga Lucia Rojas, Nathalie Simard, Douglas D. McCarthy, Siegfried Hapfelmeier, Stephen Rubino, Susan J. Robertson, Mani Larijani, Jean Gosselin, Ivaylo I. Ivanov, Alberto Martin, Rafael Casellas, Dana J. Philpott, Stephen E. Girardin, Kathy D. McCoy, Andrew J. Macpherson, Christopher J. Paige & Jennifer L. Gommerman
The largest mucosal surface in the body is in the gastrointestinal tract, a location that is heavily colonized by microbes that are normally harmless. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the gastrointestinal tract is the production and transepithelial transport of poly-reactive IgA (ref. 1). Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T-cell help, undergo class switch recombination of their immunoglobulin receptor to IgA, and differentiate to become plasma cells2. However, IgA-secreting plasma cells probably have additional attributes that are needed for coping with the tremendous bacterial load in the gastrointestinal tract. Here we report that mouse IgA+ plasma cells also produce the antimicrobial mediators tumour-necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), and express many molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA+ plasma cells can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multifunctional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNF-α and iNOS in B-lineage cells resulted in a reduction in IgA production, altered diversification of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings reveal a novel adaptation to maintaining homeostasis in the gut, and extend the repertoire of protective responses exhibited by some B-lineage cells.