Transcriptional regulation of mu and delta gene expression in bone marrow pre-B and B lymphocytes.

Newly formed B cells first express IgM and subsequently display IgD on the cell surface. This is an ontologically, as well as developmentally, regulated process because IgD is virtually absent on neonatal splenic B cells. In the present studies we have examined, by means of nascent RNA chain labeling, the relative levels of mu to delta gene transcription in bone marrow B cells, pre-B cells, and earlier progenitors of B cells. Pre-B cells were obtained from Whitlock-type long term cultures of bone marrow cells from normal and C.B17 scid mice. Both populations were found to transcribe the delta gene at very low but detectable levels. A similarly low level of delta transcription was found to occur in surface IgM-positive cells from both cultured and freshly isolated bone marrow B cells. In all populations analyzed, termination of the majority of polymerases occurred within a discrete 1-kb region located between the microM and C delta I exons. Analysis of steady state RNA indicated that long term cultured bone marrow cells from normal mice produced both 2.7-kb normal sized microM mRNA as well as 2.9-kb aberrantly spliced I mu-mRNA, whereas those from C.B17 scid mice contained only aberrant sized mu-mRNA. In contrast to these results, our previous findings with spleen cells obtained from both neonatal and adult animals showed that delta gene transcription occurs at a relatively high level. Therefore, it is possible that activation of regulatory signals that allow polymerases to progress beyond the termination site 3' of the microM exons may occur when newly formed B cells migrate from the bone marrow to the splenic environment.