Characterization of productive and sterile transcripts from the immunoglobulin heavy-chain locus: processing of...

An analysis of the sizes and sequence content of nuclear RNA transcripts of the heavy-chain locus in two B-cell lymphomas, 70Z/3 and 38C-13, and in selected hybridoma derivatives of 38C has led to the identification of two distinct precursors of the mRNAs encoding the membrane and secretory forms of mu chain. These precursors, termed Pm1 and Ps1, extend from a common 5' terminus (presumably the cap site) to alternative polyadenylation sites located 3' of the membrane and secretory tailpieces, Pm1 and Ps1 are present in similar amounts in lymphomas, indicating roughly equivalent usage of the two polyadenylation sites, whereas Ps1 much greater than Pm1 in hybridomas, indicating that mature plasma cells produce a trans-acting factor which enhances cleavage at the proximal (muS) site. The lymphomas also synthesize several nonproductive or sterile mu (Smu) transcripts from the second H allele. One class of sterile mu transcripts appears to be initiated about 1 kilobase downstream from the JH4 element. In 70Z, in which the nonproductive H allele has undergone a D1J2 fusion, another initiation site was located about 0.3 kilobase upstream of the D1 element. The sterile mu transcripts exhibit the same regulated termination at alternative polyadenylation sites as the mu mRNA precursors, although their rate of production is not necessarily coupled to that of the productive allele. This analysis has also defined probable processing pathways for productive and sterile components in which there is a 5' leads to 3' order for the excision of the large introns.