IDENTIFICATION OF AN ACTIVITY IN B-CELL EXTRACTS THAT SELECTIVELY IMPAIRS THE FORMATION OF AN IMMUNOGLOBULIN MU-S POLY(A) SITE PROCESSING COMPLEX

The immunoglobulin mu heavy-chain transcription unit is differentially expressed during B-cell development, producing mRNAs that encode secr eted (mu s) and membrane-bound (mu m) forms of the heavy-chain polypep tide. Whereas the mu s mRNA and the mu m mRNA are produced in approxim ately equal abundance in B cells, an increase in the utilization of th e mu s poly(A) site contributes to the production of the mu s mRNA as the predominant form in a plasma cell. Previous experiments have demon strated a correlation between the formation of a stable complex on a p oly(A) site and the relative function of the poly(A) site. We have thu s investigated the parameters determining the interaction of these fac tors with the immunoglobulin poly(4) sites. Assays of complex formatio n involving the two immunoglobulin poly(A) sites by using HeLa cell ac tivities revealed the formation of stable complexes with no apparent d ifference between the mu s site and the mu m site. In contrast, the mu s-specific complex was markedly less stable when a B-cell extract was used. Fractionation of B-cell extracts has revealed an activity that specifically destabilizes the mu s polyadenylation complex, suggesting that the function of this poly(A) site may be regulated by both posit ive- and negative-acting factors.