Innate and Adaptive Humoral Responses Coat Distinct Commensal Bacteria with Immunoglobulin A.
Innate and Adaptive Humoral Responses Coat Distinct Commensal Bacteria with Immunoglobulin A.
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DOI：
10.1016/j.immuni.2015.08.007
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发表时间：
2015-09-15
期刊：
影响因子：
32.4
通讯作者：
Bendelac A
中科院分区：
文献类型：
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作者：
Bunker JJ;Flynn TM;Koval JC;Shaw DG;Meisel M;McDonald BD;Ishizuka IE;Dent AL;Wilson PC;Jabri B;Antonopoulos DA;Bendelac A
免疫球蛋白A （IgA）在粘膜表面显著分泌，覆盖了一小部分肠道微生物群。然而，与IgA结合的共生细菌的特征很差，它们引发的体液免疫类型仍然难以捉摸。我们利用细菌流式细胞术结合16S rRNA基因测序（IgA- seq）在小鼠免疫缺陷模型中鉴定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，而不是细菌的身份，决定了特异性IgA的诱导。大多数共生菌引起了来自孤儿B1b谱系和B2细胞的强烈t非依赖性（TI）反应，但排除了天然抗菌B1a特异性。非典型共生菌包括分节丝状细菌和粘毛菌避开了TI反应，但引发了t依赖性IgA。这些数据证明了不同的共生细菌通过多层体液免疫的精细靶向，并揭示了B1b谱系在TI粘膜IgA反应中的特殊功能。
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.