瑞士伯尼尔大学Andrew J. Macpherson和Stephanie C. Ganal-Vonarburg课题组合作取得一项新突破。他们的研究表明粘膜或全身暴露于微生物群影响B细胞库的形成。该项研究成果在线发表在2020年8月5日的《自然》上。
使用简化模型，研究人员探究了瞬时暴露于不同微生物群的无菌小鼠中微生物群如何重塑B细胞库及其响应能力。研究人员通过深度测序重点探究了B细胞群体以及单个细胞中免疫球蛋白库的形成。暴露于微生物的肠道粘膜所产生的寡克隆不同于无菌小鼠，并且不同于静脉注射导致全身性暴露于微生物群后所产生的多样性。
剂量递增后，IgA库（主要识别细胞表面抗原）没有扩增，而全身性接触微生物使IgG库增加并可识别微生物细胞质和细胞表面抗原。暴露于微生物主要影响B细胞在记忆和浆细胞阶段特征性免疫球蛋白重链库的形成。有序地全身性暴露于不同的微生物类群可使IgG种类多样化，并促进了其他特异性反应，而依次暴露于粘膜则产生有限的重叠种类，并且会破坏初始IgA结合特异性。
这显示了免疫系统对全身性暴露的灵活反应和避免致命性败血症反应，这与暴露于粘膜后产生的受限反应之间形成对比，反映了粘膜中宿主-共生微生物的一般性质。
据介绍，微生物群定殖会显著刺激B细胞和诱导免疫球蛋白，但是具有许多菌群定殖的哺乳动物含有高度复杂和个性化的免疫球蛋白库。
附：英文原文
Title: Mucosal or systemic microbiota exposures shape the B cell repertoire
Author: Hai Li, Julien P. Limenitakis, Victor Greiff, Bahtiyar Yilmaz, Olivier Schren, Camilla Urbaniak, Mirjam Znd, Melissa A. E. Lawson, Ian D. Young, Sandra Rupp, Mathias Heikenwlder, Kathy D. McCoy, Siegfried Hapfelmeier, Stephanie C. Ganal-Vonarburg, Andrew J. Macpherson
Issue&Volume: 2020-08-05
Abstract: Colonization by the microbiota causes a marked stimulation of B cells and induction of immunoglobulin, but mammals colonized with many taxa have highly complex and individualized immunoglobulin repertoires1,2. Here we use a simplified model of defined transient exposures to different microbial taxa in germ-free mice3 to deconstruct how the microbiota shapes the B cell pool and its functional responsiveness. We followed the development of the immunoglobulin repertoire in B cell populations, as well as single cells by deep sequencing. Microbial exposures at the intestinal mucosa generated oligoclonal responses that differed from those of germ-free mice, and from the diverse repertoire that was generated after intravenous systemic exposure to microbiota. The IgA repertoire—predominantly to cell-surface antigens—did not expand after dose escalation, whereas increased systemic exposure broadened the IgG repertoire to both microbial cytoplasmic and cell-surface antigens. These microbial exposures induced characteristic immunoglobulin heavy-chain repertoires in B cells, mainly at memory and plasma cell stages. Whereas sequential systemic exposure to different microbial taxa diversified the IgG repertoire and facilitated alternative specific responses, sequential mucosal exposure produced limited overlapping repertoires and the attrition of initial IgA binding specificities. This shows a contrast between a flexible response to systemic exposure with the need to avoid fatal sepsis, and a restricted response to mucosal exposure that reflects the generic nature of host–microbial mutualism in the mucosa.
DOI: 10.1038/s41586-020-2564-6
Source: https://www.nature.com/articles/s41586-020-2564-6
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
