REGULATION OF IGM AND IGD HEAVY-CHAIN GENE-EXPRESSION - EFFECT OF ABROGATION OF INTERGENIC TRANSCRIPTIONAL TERMINATION

Early IgM(+) B cells express little or no membrane IgD due to the low abundance of delta mRNA. Extensive transcriptional termination regulat ed by sequences in the intronic region between mu and delta heavy chai n genes may be the primary reason for the lack of delta gene transcrip tion. We have examined the effect of deletion of these sequences on th e regulation of IgM and IgD heavy chain gene expression in transfectan ts as well as mice carrying this otherwise intact transgene. By run-on transcriptional measurement, we show that the delta exons are transcr ibed in bone marrow B cells from these transgenic mice. However, in sp ite of the induced premature synthesis of the full-length mu-delta tra nscript in pre-B cells, processing to delta mRNA does not occur until the lymphocytes express cell surface IgM. Therefore, during B cell dev elopment, synthesis of the full-length transcript is a necessary but n ot sufficient condition for initiation of delta mRNA synthesis. Furthe rmore, unexpectedly, the abrogation of transcriptional termination was found to also affect the processing of the primary transcript to mu M mRNA. These results show that expression of IgD in primary B cells is stringently regulated and closely linked to IgM expression.