Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Immunology Section, Lund University, Lund, Sweden.
Mucosal Immunol. 2018 May;11(3):681-692. doi: 10.1038/mi.2017.105. Epub 2017 Dec 20.
Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103CD11b (DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103CD11b (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed αβ, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.
黏膜和非黏膜部位诱导的抗体反应显示出显著的自主性。在这里，我们证明了黏膜干扰素调节因子-4（IRF4）依赖性 CD103CD11b（DP）、经典树突状细胞（cDC）在系统免疫可溶性鞭毛蛋白（sFliC）后诱导肠系膜淋巴结（MLN）中 T 依赖性免疫球蛋白 G（IgG）和免疫球蛋白 A（IgA）反应中的关键作用。相比之下，IRF8 依赖性 CD103CD11b（SP）对于这些反应不是必需的。这种反应的缺乏与 MLN、小肠固有层中完全缺乏 sFliC 特异性浆细胞，以及令人惊讶的骨髓（BM）中完全缺乏 sFliC 特异性浆细胞有关。在免疫野生型小鼠的 BM 中积累的许多 sFliC 特异性浆细胞表达 αβ，这表明其起源于黏膜。总之，这些结果表明黏膜 DP cDC 有助于在 BM 中产生 sFliC 特异性浆细胞池，从而作为连接黏膜和系统免疫系统的桥梁。
