Transcriptional and posttranscriptional control of immunoglobulin mRNA production during B lymphocyte development

Abstract

A variety of cell lines representing different maturation stages of the B lymphocyte were used to analyse developmental changes in the transcriptional pattern through the mu-delta locus and the relationship between mu mRNA accumulation and transcriptional activity. As anticipated from earlier studies, we observed that RNA polymerase loading in the region between the mu m cleavage/poly A addition site and the delta 1 exon is markedly decreased in IgM secreting cells compared to cells bearing surface IgM or surface IgM and IgD. In several IgM secreting hybridomas, transcriptional termination mainly occurred downstream of the first mu m exon. Thus, the predominance of mu s-terminated transcripts in these cells would appear to be principally determined by RNA processing events, most likely by more efficient cleavage at the mu s poly A site and/or less efficient splicing of the C mu and mu m exons. In two plasmacytoma lines, polymerase unloading between the mu s and mu m sites also contributed significantly to the high mu s mRNA phenotype. Our results further indicate that posttranscriptional regulation is largely responsible for the greatly increased accumulation of mu mRNA in the IgM secretors. Interestingly, the sterile-mu RNA components do not seem to be subject to this posttranscriptional regulation.