Cell-specific expression of secreted versus membrane forms of immunoglobulin gamma 2b mRNA involves selective use of alternate polyadenylation sites.

Immunoglobulin heavy chain genes encode at least two forms of mRNA, secretory- and membrane-specific. In less mature B cells and tumors arising from them, lymphomas, the membrane form of the protein and mRNA are in high abundance, while in more mature stages, plasma cells, and myeloma tumor cells, the secreted forms of protein and mRNA predominate. In myeloma cells producing approximately 8:1 ratios of secretory- to membrane-encoding forms of gamma-heavy chain mRNA, we observed equimolar transcription of the secretory- and membrane-encoding exons of the gene. In isolated nuclei from 4T001 (gamma 2b) and K23 (gamma 2a) myeloma cells, the secretory-encoding mRNA polyadenylation site was used at least three times as often as the membrane-encoding mRNA polyadenylation site. In the A20 (gamma 2a) lymphoma, which produces equal amounts of mature secretory- and membrane-encoding heavy chain mRNAs, results of experiments with isolated nuclei showed that the membrane mRNA polyadenylation site was used about two times as often as the secretory mRNA polyadenylation site. Selective use of alternate polyadenylation and cleavage sites, therefore, can modulate the production of the two mRNAs from a single gene during B cell differentiation.