Regulation of usage of membrane and secreted 3' termini of alpha mRNA differs from mu mRNA.

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.