Bunker Jeffrey J, Erickson Steven A, Flynn Theodore M, Henry Carole, Koval Jason C, Meisel Marlies, Jabri Bana, Antonopoulos Dionysios A, Wilson Patrick C, Bendelac Albert
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Science. 2017 Oct 20;358(6361). doi: 10.1126/science.aan6619. Epub 2017 Sep 28.
Large quantities of immunoglobulin A (IgA) are constitutively secreted by intestinal plasma cells to coat and contain the commensal microbiota, yet the specificity of these antibodies remains elusive. Here we profiled the reactivities of single murine IgA plasma cells by cloning and characterizing large numbers of monoclonal antibodies. IgAs were not specific to individual bacterial taxa but rather polyreactive, with broad reactivity to a diverse, but defined, subset of microbiota. These antibodies arose at low frequencies among naïve B cells and were selected into the IgA repertoire upon recirculation in Peyer's patches. This selection process occurred independent of microbiota or dietary antigens. Furthermore, although some IgAs acquired somatic mutations, these did not substantially influence their reactivity. These findings reveal an endogenous mechanism driving homeostatic production of polyreactive IgAs with innate specificity to microbiota.
大量免疫球蛋白A（IgA）由肠道浆细胞组成性分泌，以包裹并容纳共生微生物群，但这些抗体的特异性仍然难以捉摸。在这里，我们通过克隆和表征大量单克隆抗体来分析单个小鼠IgA浆细胞的反应性。IgA并非对单个细菌分类群具有特异性，而是具有多反应性，对微生物群的一个多样但特定的子集具有广泛反应性。这些抗体在幼稚B细胞中出现的频率较低，并在派尔集合淋巴结中再循环时被选入IgA库。这种选择过程独立于微生物群或饮食抗原发生。此外，尽管一些IgA获得了体细胞突变，但这些突变并未实质性影响它们的反应性。这些发现揭示了一种内源性机制，驱动对微生物群具有固有特异性的多反应性IgA的稳态产生。
