Selective adherence of IgA to murine Peyer's patch M cells:: Evidence for a novel IgA receptor

Selective adherence of IgA to murine Peyer's patch M cells:: Evidence for a novel IgA receptor
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DOI:
10.4049/jimmunol.169.4.1844
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发表时间:
2002-08-15
影响因子:
4.4
通讯作者:
Neutra, MR
Neutra, MR
中科院分区:
医学2区
文献类型:
--
作者:
Mantis, NJ;Cheung, MC;Neutra, MR

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被引文献

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M细胞代表粘膜Ag穿过肠上皮运输并递送到下面的肠相关淋巴组织的主要途径。在啮齿动物和兔中,派伊尔集合淋巴结M细胞选择性结合和内吞分泌伊加(SIgA)Ab。M细胞IgR的性质和参与这种相互作用的SIgA结构域都不清楚。使用小鼠连接回肠环测定,我们发现,单克隆伊加抗体与或不与分泌成分,但不是IgG或IgM抗体,结合到派尔氏结M细胞的顶面,表明受体是特异性的伊加同种型。人血清伊加和初乳SIgA也结合小鼠M细胞。无唾液酸糖蛋白受体或其他凝集素样受体未检测到的顶面的M细胞。我们使用重组人IgA 1和人IgA 2抗体和结构域交换伊加/IgG嵌合体,以确定这两个域Calpha 1和Calpha 2是必需的伊加粘附到小鼠派伊尔氏斑M细胞。这将M细胞伊加受体与结合结构域Calpha 2-Calpha 3的CD 89(FcalphaI)区分开。最后,我们通过免疫荧光显微镜观察到人回肠中的一些M细胞被伊加包被。总之,这些数据表明,小鼠,可能是人类,M细胞表达的IgA特异性受体在其顶端表面介导的跨上皮运输的SIgA从肠腔到下面的肠道相关的有组织的淋巴组织。
M cells represent the primary route by which mucosal Ags are transported across the intestinal epithelium and delivered to underlying gut-associated lymphoid tissues. In rodents and rabbits, Peyer's patch M cells selectively bind and endocytose secretory IgA (SIgA) Abs. Neither the nature of the M cell IgR nor the domains of SIgA involved in this interaction are known. Using a mouse ligated ileal loop assay, we found that monoclonal IgA Abs with or without secretory component, but not IgG or IgM Abs, bound to the apical surfaces of Peyer's patch M cells, indicating that the receptor is specific for the IgA isotype. Human serum IgA and colostral SIgA also bound to mouse M cells. The asialoglycoprotein receptor or other lectin-like receptors were not detected on the apical surfaces of M cells. We used recombinant human IgA1 and human IgA2 Abs and domain swapped IgA/IgG chimeras to determine that both domains Calpha1 and Calpha2 are required for IgA adherence to mouse Peyer's patch M cells. This distinguishes the M cell IgA receptor from CD89 (FcalphaI), which binds domains Calpha2-Calpha3. Finally, we observed by immunofluorescence microscopy that some M cells in the human ileum are coated with IgA. Together these data suggest that mouse, and possibly human, M cells express an IgA-specific receptor on their apical surfaces that mediates the transepithelial transport of SIgA from the intestinal lumen to underlying gut-associated organized lymphoid tissues.