The requirements for IgM assembly and secretion were evaluated by introducing a constitutively expressed J-chain cDNA into lymphoid and nonlymphoid cell lines expressing the secretory form of monomer IgM. Assays of cell lysates and supernatants showed that only secretory monomer IgM is required for the synthesis and secretion of hexamer IgM, whereas J chain, as well as the secreted form of monomer, is required for the synthesis and secretion of pentamer IgM. Moreover, J chain facilitates the polymerization process so that pentamer IgM is preferentially synthesized. Other components of the polymerization process were found to be shared by all the cell lines examined, whether the cells were of lymphoid or nonlymphoid origin and had a rudimentary or developed secretory apparatus. These results identify monomer IgM and J chain as the two components that determine the B-cell-specific expression of IgM antibodies and, thus, as the appropriate targets for therapeutic regulation of IgM responses.In a primary immune response, a resting B cell is triggered by antigen and successive cytokine signals to differentiate into a blast cell that secretes pentamer IgM antibody. Analyses of the response have identified the de novo synthesis of the pentamer joining protein, the J chain, as a critical step in the differentiative process (1). The evidence is based in part on structural studies which revealed that J chain is incorporated exclusively into the pentameric form of IgM (2). Within the pentamer it links two monomer subunits through disulfide bonds between cysteines at positions 14 and 68 of the J chain and the penultimate cysteines of opposing p. heavy chains (3, 4).Evidence for the role of J chain is also based on the responses of B-cell lines to J-chain gene expression. B lymphomas expressing receptors for interleukin 2 or 5 can be induced by cytokine treatment to amplify J-chain gene transcription and, as a consequence, to markedly increase secretion of IgM (5-7). Moreover, B-cell lymphoma lines can be converted to IgM secretors by transfection with a J-chain cDNA (2) or by fusion with an IgG-secreting myeloma that expresses the J chain (8, 9).Although the expression of J chain correlates strongly with pentamer IgM synthesis, several questions remain concerning the actual function of the J polypeptide in the polymerization process. First, is J chain required for pentamer assembly, or does it simply facilitate closing of the polymer at the pentamer stage? Second, does the expression of J chain in turn induce changes in other B-cell components that contribute to IgM assembly and secretion? These questions were addressed in the present study by transfecting the murine J-chain cDNA into a series of B lymphomas representing successive stages in B-cell differentiation and transfecting all three pentamer components into a nonlymphoid cell line. Here we present evidence that (i) J chain is required for the synthesis of the pentamer, but not the hexamer form of IgM, (ii) its expression is regulated independently of the oth...