Bunker Jeffrey J, Flynn Theodore M, Koval Jason C, Shaw Dustin G, Meisel Marlies, McDonald Benjamin D, Ishizuka Isabel E, Dent Alexander L, Wilson Patrick C, Jabri Bana, Antonopoulos Dionysios A, Bendelac Albert
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Biosciences Division, Argonne National Laboratory, Argonne, IL 60439, USA; Computation Institute, University of Chicago, Chicago, IL 60637, USA.
Immunity. 2015 Sep 15;43(3):541-53. doi: 10.1016/j.immuni.2015.08.007. Epub 2015 Aug 25.
Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses.
免疫球蛋白A（IgA）主要在黏膜表面分泌，并覆盖一部分肠道微生物群。然而，与IgA结合的共生细菌的特征尚不明确，它们引发的体液免疫类型也仍不清楚。我们在免疫缺陷小鼠模型中使用细菌流式细胞术结合16S rRNA基因测序（IgA-Seq）来鉴定与IgA结合的细菌，并阐明共生IgA靶向的机制。我们发现，在小肠中的驻留而非细菌种类决定了特异性IgA的诱导。大多数共生菌引发了强烈的非T细胞依赖性（TI）反应，这些反应源自孤儿B1b谱系和B2细胞，但不包括天然抗菌的B1a特异性。包括分节丝状菌和黏液螺旋菌在内的非典型共生菌逃避了TI反应，但引发了T细胞依赖性IgA。这些数据表明体液免疫的多层机制对不同共生细菌具有精确的靶向作用，并揭示了B1b谱系在TI黏膜IgA反应中的特殊功能。
