REGULATION OF USAGE OF MEMBRANE AND SECRETED 3' TERMINI OF ALPHA MESSENGER-RNA DIFFERS FROM MU MESSENGER-RNA

Previous studies demonstrated that the addition of transforming growth factor-beta (TGF-beta) to LPS-stimulated B cell cultures induced cells to express membrane IgA and to mature to IgA-secreting cells without a parallel change in usage of 3' termini by alpha-mRNA. In these cultures, the secreted form of alpha-MRNA was predominant even before expression of membrane IgA could be detected. In the present study, we demonstrate that the preferential usage of the secreted terminus of alpha-mRNA in these cultures is not caused by transcription termination and reflects a difference in the regulation of choice of 3' terminus for alpha and mu-mRNA. The addition of TGF-beta to LPS-stimulated cultures causes an increase in the steady state level of alpha-mRNA using the secreted 3' terminus. in contrast, TGF-beta decreases the steady state level of mu-mRNA and inhibits usage of the 3' terminus for the secreted form of mu, suggesting that the choice of 3' terminus for alpha and mu-mRNA is regulated differently in LPS-stimulated cultures. To determine whether the difference in usage of 3' termini by alpha and mu-mRNA was a property of the culture system or whether it reflected a difference in regulation, C(alpha) was transfected into cell lines representing different stages of B cell development. The secreted form of alpha-mRNA predominates regardless of the ratio of membrane to secreted forms of the endogenous C(mu) gene. A similar dichotomy in 3' terminus usage occurred in a stable C(alpha) transfectant of the BCL1 lymphoma, suggesting that trans-acting factors are not limiting. Furthermore, as was the case with normal B cells, the predominance of the secreted form of the transfected C(alpha) genes was not due to transcription termination. These data demonstrate that usage of 3' terminus in alpha and mu-mRNA is regulated differently.