Koshland M E
Annu Rev Immunol. 1985;3:425-53. doi: 10.1146/annurev.iy.03.040185.002233.
During the last decade the immunoglobulin J chain has indeed come of age. The amino-acid sequence has been determined for the mouse and human polypeptides, and the data obtained have established the uniqueness of the primary structure and its high degree of conservation in vertebrates. The biosynthesis of J chain has been defined: The information is encoded in a simple transcription unit that is induced by changes in chromatin structure to express a single primary transcript and a single mature message; translation of the message yields a propolypeptide which is processed and transported through the cell by the conventional pathway for secreted proteins. As a result of these advances, many of the functions of the J chain have been clarified. Analyses of the expression of J chain mRNA and protein in mouse lymphocytes have shown that the initiation and amplification of J-chain synthesis are critical steps in the pentamer IgM response because the J polypeptide is required for the assembly of the IgM antibody. Analyses of the behavior of the polymeric Igs have established that the J-chain component contributes, certainly indirectly and perhaps also directly, to the secretion of pentamer IgM and the transcellular transport of both IgM and IgA. However, knowledge of the J chain has yet to achieve full maturity. How the J chain participates in the polymerization of IgM and IgA needs to be reexamined in view of the recent findings that assembly may involve an oxidative mechanism catalyzed by a lymphocyte-specific enzyme. The observation that J chain may be constitutively expressed in human B cells and the possibility that J chain performs additional regulatory functions in monomer-Ig secreting cells should be pursued. Determination of the J-chain secondary structure and its arrangement in the polymer Fc domains is critical to understanding the effector functions of polymer Ig. Lastly, the finding that late-acting factors, such as interleukin-2, induce an amplification in J-chain synthesis opens the way to using the expression of J chain as a model system for dissecting the mechanism of gene regulation. These are the challenges for the next decade.
在过去十年里，免疫球蛋白J链确实已步入成熟阶段。小鼠和人类多肽的氨基酸序列已被确定，所获数据证实了其一级结构的独特性及其在脊椎动物中的高度保守性。J链的生物合成已得到明确：信息编码在一个简单的转录单元中，该转录单元由染色质结构变化诱导，以表达单一的初级转录本和单一的成熟信使RNA；信使RNA的翻译产生一种前体多肽，该前体多肽通过分泌蛋白的常规途径进行加工和细胞内运输。由于这些进展，J链的许多功能已得到阐明。对小鼠淋巴细胞中J链mRNA和蛋白质表达的分析表明，J链合成的起始和扩增是五聚体IgM反应中的关键步骤，因为J多肽是IgM抗体组装所必需的。对聚合免疫球蛋白行为的分析表明，J链成分肯定间接且可能也直接有助于五聚体IgM的分泌以及IgM和IgA的跨细胞转运。然而，对J链的认识尚未完全成熟。鉴于最近的发现表明组装可能涉及淋巴细胞特异性酶催化的氧化机制，J链如何参与IgM和IgA的聚合需要重新审视。J链可能在人类B细胞中组成性表达这一观察结果以及J链在分泌单体Ig的细胞中发挥额外调节功能的可能性值得深入研究。确定J链的二级结构及其在聚合物Fc结构域中的排列对于理解聚合免疫球蛋白的效应功能至关重要。最后，诸如白细胞介素-2等后期作用因子诱导J链合成扩增这一发现为将J链的表达用作剖析基因调控机制的模型系统开辟了道路。这些是未来十年面临的挑战。
