1月12日,国际著名杂志Nature在线刊登了加拿大多伦多大学研究人员的最新研究成果“Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut”,文章中,作者通过研究揭示了肠道淋巴细胞的重要作用。
淋巴细胞是白细胞的一种。由淋巴器官产生,机体免疫应答功能的重要细胞成分。淋巴器官根据其发生和功能的差异,可分为中枢淋巴器官和周围淋巴器官两类。前者包括胸腺、腔上囊或其相当器官(有人认为在哺乳动物是骨髓)。它们无须抗原刺激即可不断增殖淋巴细胞,成熟后将其转送至周围淋巴器官。后者包括脾、淋巴结等。成熟淋巴细胞需依赖抗原刺激而分化增殖,继而发挥其免疫功能。
肠道含有大量对生物体健康来说所必需的细菌,但也是淋巴细胞的一个丰富来源,后者的存在是为了消除感染。淋巴细胞怎样不让自己去攻击有益菌、同时又能够对真正的病原体做出反应?Fritz等人发现,在B-细胞分化成肠道中的浆细胞时,它们采取一种与先天免疫细胞相似的表现型(炎性单核细胞),同时保持自己生成免疫球蛋白的能力。这样在固有层中所产生的“免疫球蛋白-A分泌浆细胞”,被发现是在小肠细菌和免疫系统之间维持平衡所需的抗菌调控物质“肿瘤坏死因子-α”和“可诱导性一氧化氮合成酶”的一个主要来源。(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.