The secretory form of the IgM heavy chain (MI) is produced at all stages of B cell development, but IgM is only efficiently secreted as polymers by plasma cells. We have addressed the question of why u, chains are not secretion competent at other stages of B cell development. In pre-B cells, membrane u chains can mature through the secretory pathway when complexed with the surrogate light chain. While u,containing complexes form higher-order polymers, these are never assembled into completed covalent pentameric or hexameric structures, and are rapidly degraded. To identify the sequences on u, chains responsible for their retention and degradation, we generated stable transfectants of a u-negative pre-B cell line expressing either wild-type or mutant p, constructs. Wild-type u, proteins were not secreted by these cells. However, u, proteins containing one or more mutations in the secretory tailpiece, allowing them to escape thiol-retention, were released from the endoplasmic reticulum and matured through the secretory pathway. The surrogate light chain proteins, X5 and VpreB, were coprecipitated as a complex with u.. We conclude that u. chains are retained during all stages of B cell development by a thiol-mediated retention mechanism. The failure of pre-B cells to secrete u.-containing complexes is due to the rapid degradation of retained u, proteins, and not to any innate inability of pre-B cells to either polymerize or secrete the pre-B cell receptor.
|Publication status||Published - 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology