中文摘要：通过粘膜分泌的二聚体IgA对非致病性微生物群作出反应，是哺乳动物产生抗体的主要原因。在多克隆黏膜IgA抗体应答中可以检测到多种结合特异性，但单克隆杂交瘤在将抗原特异性或多反应结合与体内微生物生理功能效应联系起来方面的研究有限。本研究使用重组二聚体单克隆IgAs (mIgAs)来精细绘制小鼠肠道浆细胞对单个微生物定植的反应，鉴定了一系列针对表面和非表面膜抗原的抗原特异性mIgA分子。在体内，针对不同抗原的单个二聚体mIgAs的分泌通过特异性结合显示出肠道细菌功能和代谢的明显改变。即使在以相同微生物抗原为靶点的情况下，微生物代谢改变也因IgA表位特异性而异。相比之下，细菌表面涂层通常会降低运动能力，限制胆汁酸毒性。因此，对单一微生物的整体肠道IgA反应包含平行成分，对微生物碳源摄取、噬菌体敏感性、运动性和膜完整性具有显著影响。
外文摘要：Dimeric IgA secreted across mucous membranes in response to nonpathogenic taxa of the microbiota accounts for most antibody production in mammals. Diverse binding specificities can be detected within the polyclonal mucosal IgA antibody response(1-10), but limited monoclonal hybridomas have been studied to relate antigen specificity or polyreactive binding to functional effects on microbial physiology in vivo(11-17). Here we use recombinant dimeric monoclonal IgAs (mIgAs) to finely map the intestinal plasma cell response to microbial colonization with a single microorganism in mice. We identify a range of antigen-specific mIgA molecules targeting defined surface and nonsurface membrane antigens. Secretion of individual dimeric mIgAs targeting different antigens in vivo showed distinct alterations in the function and metabolism of intestinal bacteria, largely through specific binding. Even in cases in which the same microbial antigen is targeted, microbial metabolic alterations differed depending on IgA epitope specificity. By contrast, bacterial surface coating generally reduced motility and limited bile acid toxicity. The overall intestinal IgA response to a single microbe therefore contains parallel components with distinct effects on microbial carbon-source uptake, bacteriophage susceptibility, motility and membrane integrity.
外文关键词：ESCHERICHIA-COLI；IMMUNOGLOBULIN-A；B-CELLS；HUMAN GUT；OMPC；EXPRESSION；ANTIBODIES；TRANSPORT；BACTERIA；DRIVES
作者：Rollenske, T；Burkhalter, S；Muerner, L；von Gunten, S；Lukasiewicz, J；Wardemann, H；Macpherson, AJ
作者单位：Univ Bern；Ludwik Hirszfeld Inst Immunol & Expt Therapy；German Canc Res Ctr
期刊名称：NATURE
期刊影响因子：42.779
出版年份：2021
出版刊次：
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