MECHANISM FOR TRANSFORMING GROWTH-FACTOR-BETA REGULATION OF ALPHA-MESSENGER-RNA IN LIPOPOLYSACCHARIDE-STIMULATED B-CELLS

Transforming growth factor (TGF)-beta has been shown to stimulate isot ype switching to IgA in cultures of lipopolysaccharide (LPS)-stimulate d B cells. The induction of isotype switching is associated with the a ppearance of novel germline a transcripts that cannot be found in cult ures stimulated with LPS alone. TGF-beta also increases the steady sta te level of productive alpha mRNA. In order to further elucidate both the role of TGF-beta and germline transcripts in isotype switching to IgA in B cells, the mechanism responsible for the changes in alpha mRN A was investigated. The increase in alpha mRNA which does not occur un til day 2 of culture continues until at least day 4. Nuclear run-on an alysis demonstrated that TGF-P does not significantly increase the rat e of transcription of either germline or productive alpha mRNA after 1 2, 24, or 48 h of culture. However, by day 2 of culture TGF-beta incre ases the half-life of alpha mRNA. These findings support the idea that TGF-beta acts as a secondary signal to stimulate isotype switching to IgA in a population that has already received a signal that drives it toward IgA production. In addition these studies suggest that either the germline transcripts or processing of pre-germline alpha mRNA tran scripts plays a role in targeting recombination.