Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut.
Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut.
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DOI：
10.1038/nature10698
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发表时间：
2011-12-11
期刊：
影响因子：
64.8
通讯作者：
Gommerman, Jennifer L.
中科院分区：
文献类型：
--
作者：
Fritz, Joerg H.;Rojas, Olga Lucia;Simard, Nathalie;McCarthy, Douglas D.;Hapfelmeier, Siegfried;Rubino, Stephen;Robertson, Susan J.;Larijani, Mani;Gosselin, Jean;Ivanov, Ivaylo I.;Martin, Alberto;Casellas, Rafael;Philpott, Dana J.;Girardin, Stephen E.;McCoy, Kathy D.;Macpherson, Andrew J.;Paige, Christopher J.;Gommerman, Jennifer L.
身体中最大的粘膜表面是在胃肠道（GI）中，该位置被通常无害的微生物大量定殖。维持这种微生物负荷和密集分布在胃肠道中的淋巴细胞之间的稳态平衡所需的关键机制是多反应性伊加的产生和跨上皮转运。在粘膜组织内，B细胞对细胞因子产生应答，有时在没有T细胞帮助的情况下，经历其免疫球蛋白（IG）受体到伊加的类别转换重组（CSR），并分化为浆细胞（PC）。然而，分泌IgA的PC可能具有应对胃肠道中巨大细菌负荷所需的额外属性。在这里，我们报告说，伊加+ PC也产生抗微生物介质TNFα和iNOS，并表达许多分子，通常与单核细胞/粒细胞类型。在存在肠道基质的情况下，可以在体外重演产生iNOS的伊加+ PC的发育，并且这种体内和体外多功能表型的获得依赖于微生物共刺激。B系细胞中TNFα和iNOS的缺失导致伊加产生减少，肠道微生物群的多样化改变以及肠道嗜性病原体的清除不良。这些发现揭示了维持肠道内稳态的新适应，并扩展了一些B谱系细胞所表现出的保护性反应的全部功能。
The largest mucosal surface in the body is in the gastrointestinal (GI) tract, a location that is heavily colonized by normally harmless microbes. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the GI tract is the production and trans-epithelial transport of poly-reactive IgA. Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T cell help, undergo class switch recombination (CSR) of their Immunoglobulin (Ig) receptor to IgA, and differentiate to become plasma cells (PC). However, IgA-secreting PC likely have additional attributes that are needed for coping with the tremendous bacterial load in the GI tract. Here we report that IgA+ PC also produce the anti-microbial mediators TNFα and iNOS, and express many molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA+ PC can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multi-functional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNFα 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.
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DOI：
10.1084/jem.20101715
发表时间：
2011-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kelly-Scumpia KM;Scumpia PO;Weinstein JS;Delano MJ;Cuenca AG;Nacionales DC;Wynn JL;Lee PY;Kumagai Y;Efron PA;Akira S;Wasserfall C;Atkinson MA;Moldawer LL
通讯作者：
Moldawer LL
影响因子：
32.4
作者：
Neves, Patricia;Lampropoulou, Vicky;Fillatreau, Simon
通讯作者：
Fillatreau, Simon
DOI：
10.1016/j.bbrc.2011.06.035
发表时间：
2011-07-08
影响因子：
3.1
作者：
Lee, Mi-Ra;Seo, Goo-Young;Kim, Pyeung-Hyeun
通讯作者：
Kim, Pyeung-Hyeun
影响因子：
30.3
作者：
Peterson, Daniel A.;McNulty, Nathan P.;Gordon, Jeffrey I.
通讯作者：
Gordon, Jeffrey I.
DOI：
10.1073/pnas.0307317101
发表时间：
2004-02-17
影响因子：
11.1
作者：
Suzuki, K;Meek, B;Fagarasan, S
通讯作者：
Fagarasan, S