The coming of age of the immunoglobulin J chain

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.