Regulation of usage of membrane and secreted 3' termini of alpha mRNA differs from mu mRNA
Lebman, D.A.; Park, M.J.; Fatica, R.; Zhang, Z.
Journal of Immunology 148(10): 3282-3289
1992
ISSN/ISBN: 0022-1767 PMID: 1578149 Document Number: 401835
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 with out a parallel change in usage of 3' termini by .alpha.-mRNA. In these cultures, the secreted form of .alpha. RNA 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 different in regulation, C.alpha. was transfected into cell lines representing different stage 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.