Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan.
Nat Immunol. 2016 Sep;17(9):1109-17. doi: 10.1038/ni.3508. Epub 2016 Jul 18.
Aberrant production of IgE antibodies can lead to allergic diseases. Normally, IgE(+) B cells rarely differentiate into memory B cells (Bmem) or long-lived plasma cells (LLPCs), as they only transiently participate in the germinal center (GC), but the mechanism behind this remains elusive. We found that membrane IgE (mIgE) autonomously triggered rapid plasma-cell differentiation and apoptosis independently of antigen or cellular context, predominantly through the mutually independent CD19-PI3K-Akt-IRF4 and BLNK-Jnk/p38 pathways, respectively, and we identified the ectodomains of mIgE as being responsible. Accordingly, deregulated GC IgE(+) B cell proliferation and prolonged IgE production with exaggerated anaphylaxis were observed in CD19- and BLNK-deficient mice. Our findings reveal an autonomous mIgE signaling mechanism that normally prevents IgE(+) Bmem and LLPC formation, providing insights into the molecular pathogenesis of allergic diseases.
异常的 IgE 抗体产生可导致过敏疾病。通常，IgE(+) B 细胞很少分化为记忆 B 细胞（Bmem）或长寿浆细胞（LLPC），因为它们仅短暂参与生发中心（GC），但其背后的机制仍不清楚。我们发现膜 IgE（mIgE）自主触发快速浆细胞分化和凋亡，与抗原或细胞环境无关，主要分别通过相互独立的 CD19-PI3K-Akt-IRF4 和 BLNK-Jnk/p38 途径，并且我们确定 mIgE 的胞外结构域是负责的。因此，在 CD19 和 BLNK 缺陷小鼠中观察到 GC IgE(+) B 细胞增殖不受调节和 IgE 产生延长，伴有过敏反应加剧。我们的发现揭示了一种自主的 mIgE 信号机制，通常可防止 IgE(+) Bmem 和 LLPC 的形成，为过敏疾病的分子发病机制提供了新的见解。
