Winsauer Caroline, Prepens Sandra, Schlienz Dirk, Nedospasov Sergei, Kruglov Andrey A
German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin 10117, Germany.
German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin 10117, Germany; Belozersky Institute of Physico-Chemical Biology and Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
J Immunol Methods. 2015 Jun;421:54-60. doi: 10.1016/j.jim.2015.03.001. Epub 2015 Mar 17.
Commensal microbiota at the mucosal surfaces controls multiple aspects of body homeostasis. Therefore, regulation of microflora composition by the host is crucial, and one of the mechanisms driving microbiota diversity is the production of large quantities of immunoglobulin A (IgA) at the mucosal surfaces. However, mechanisms of IgA induction in the gut are not completely understood. Here we further characterize a mouse model for studying T cell-dependent IgA production in the gut due to specific genetic ablation of LTβ in RORγt+ cells. Using in utero blockade of the mesenteric lymph node development, we showed that IgA induction in these mice occurs directly in the LP. Furthermore, T cell-dependent IgA inducing mechanism in these mice generates distinct IgA plasma cells producing commensal microflora-binding IgA antibodies. Thus, this model represents a unique in vivo tool for the analysis of T cell-dependent IgA plasma cell generation and their antibody specificity.
黏膜表面的共生微生物群控制着身体内环境稳定的多个方面。因此,宿主对微生物群落组成的调节至关重要,而驱动微生物群多样性的机制之一是在黏膜表面产生大量免疫球蛋白A(IgA)。然而,肠道中IgA诱导的机制尚未完全明确。在此,我们进一步描述了一种小鼠模型,该模型用于研究由于RORγt+细胞中LTβ的特异性基因缺失而导致的肠道中T细胞依赖性IgA产生。通过子宫内阻断肠系膜淋巴结发育,我们发现这些小鼠中的IgA诱导直接发生在固有层。此外,这些小鼠中T细胞依赖性IgA诱导机制产生了不同的IgA浆细胞,这些浆细胞产生与共生微生物群结合的IgA抗体。因此,该模型是分析T细胞依赖性IgA浆细胞产生及其抗体特异性的独特体内工具。