Alternative expression of secreted and membrane forms of immunoglobulin mu-chain is regulated by transcriptional termination in stable plasmacytoma transfectants

Abstract

During B cell differentiation the mu H chain of IgM is produced initially as a cell surface (m) and later as a secreted (s) form. Production of either the secreted (microseconds) or the membrane (micron) mRNA results from selection of either the promoter proximal (microseconds) or distal (micron) poly(A)/cleavage site. We have transfected lymphoid cell lines of disparate developmental stages with productively rearranged Ig mu-chain constructs to determine the mechanism by which alternative 3' end selection is achieved. Stable transfectants of lymphomas (early stage, microseconds less than or equal to micron) and a plasmacytoma (late stage, microsecond much greater than micron) produce the anticipated levels of microsecond and micron mRNA. Transcription termination between the microsecond and micron poly(A) sites occurs only in the plasmacytoma transfectants, and appears to be the rate-limiting step in the production of the final steady state microsecond/micron mRNA ratio. We propose that as the B cell becomes terminally committed to secretion, the mechanism responsible for the regulation of the steady state microsecond/micron mRNA ratio shifts from exclusively post-transcriptional to predominantly transcriptional termination.