Polymeric IgM immunoglobulins have high avidity for antigen and complement, and dominate primary antibody responses. They are produced either as assemblies of six µ2L2 subunits (i.e., hexamers), or as pentamers of two µ2L2 subunits and an additional protein termed J-chain (JC), which allows transcytosis across epithelia. The molecular mechanism of IgM assembly with the desired stoichiometry remained unknown. Here, we show in vitro and in cellula that JC outcompetes the sixth IgM subunit during assembly. Before insertion into IgM, JC exists as an ensemble of largely unstructured, protease-sensitive species with heterogeneous, non-native disulfide bonds. The J-chain interacts with the hydrophobic β-sheets selectively exposed by nascent pentamers. Completion of an amyloid-like core triggers JC folding and drives disulfide rearrangements that covalently stabilize JC-containing pentamers. In cells, the quality control factor ERp44 surveys IgM assembly and prevents the secretion of aberrant conformers. This mechanism allows the efficient production of high-avidity IgM for systemic or mucosal immunity.

中文翻译：

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J 链如何确保免疫球蛋白 IgM 五聚体的组装。


聚合物 IgM 免疫球蛋白对抗原和补体具有高亲和力，并主导一抗反应。它们以 6 个 μ2L2 亚基（即六聚体）的组装体形式产生，或以 2 个 μ2L2 亚基和一种称为 J 链 （JC） 的附加蛋白质的五聚体形式产生，该蛋白允许跨上皮细胞进行转胞吞作用。IgM 组装与所需化学计量的分子机制仍然未知。在这里，我们在体外和纤维素中表明 JC 在组装过程中超过了第六个 IgM 亚基。在插入 IgM 之前，JC 以大部分非结构化、蛋白酶敏感物种的集合形式存在，具有异质性、非天然二硫键。J 链与新生五聚体选择性暴露的疏水性 β 片相互作用。淀粉样蛋白核心的完成触发 JC 折叠并驱动二硫键重排，共价稳定含 JC 的五聚体。在细胞中，质量控制因子 ERp44 检查 IgM 组装并防止异常构象异构体的分泌。这种机制允许高效产生高亲和力 IgM 以实现全身或粘膜免疫。