Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Center for Clinical and Translational Research, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Cell Rep. 2018 Feb 13;22(7):1824-1834. doi: 10.1016/j.celrep.2018.01.048.
Helminth infection is known for generating large amounts of poly-specific IgE. Here we demonstrate that innate-like B1 cells are responsible for this IgE production during infection with the nematode parasites Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. In vitro analysis of B1 cell immunoglobulin class switch recombination to IgE demonstrated a requirement for anti-CD40 and IL-4 that was further enhanced when IL-5 was added or when the B1 source was helminth infected mice. An IL-25-induced upregulation of IgE in B1 cells was also demonstrated. In T cell-reconstituted RAG1 mice, N. brasiliensis clearance was enhanced with the addition of B2 cells in an IgE-dependent manner. This enhanced clearance was impeded by reconstitution with IgE sufficient B1 cells. Mucosal mast cells mediated the B2 cell enhancement of clearance in the absence of B1 cells. The data support B1 cell IgE secretion as a regulatory response exploited by the helminth.
寄生虫感染会导致大量多特异性 IgE 的产生。在这里,我们证明了固有样 B1 细胞在感染巴西旋毛虫和柏氏嗜碘线虫时负责产生这种 IgE。对 B1 细胞免疫球蛋白类别转换重组为 IgE 的体外分析表明,抗 CD40 和 IL-4 的需求是必需的,当添加 IL-5 或当 B1 来源是感染寄生虫的小鼠时,这种需求进一步增强。还证明了 IL-25 诱导 B1 细胞 IgE 的上调。在 T 细胞重建的 RAG1 小鼠中,通过 IgE 依赖性方式添加 B2 细胞可增强 N. brasiliensis 的清除。用 IgE 充足的 B1 细胞重建会阻碍这种增强的清除。在没有 B1 细胞的情况下,黏膜肥大细胞介导了 B2 细胞清除的增强。这些数据支持 B1 细胞 IgE 分泌是寄生虫利用的一种调节反应。