Transcriptional regulation of the mu-delta heavy chain locus in normal murine B lymphocytes.

The heavy chain genes for IgM (C mu) and IgD (C delta) are expressed differentially during B cell maturation and activation. We have determined the role that transcription plays in the regulation of these changes by using the method of in vitro nascent RNA chain elongation. In neonatal cells that express much lower densities of IgD than IgM on their surface, transcription of C delta is observed at half the level of C mu. This 3:1 transcriptional ratio of mu to delta is preserved in mature resting cells, which express higher densities of IgD on the surface than IgM. When activated by the mitogen, lipopolysaccharide (LPS), transcription of C mu is preferentially enhanced. However, C delta transcription is not shut off even though the expression of IgD in the stimulated cells is greatly decreased. In all three differentiative stages, polymerase unloading occurs in the vicinity of a large inverted repeat sequence, 5' to C delta and 3' to the mu membrane exons. This suggests that the developmental selection of secreted vs. membrane-bound carboxyl-terminal exons is controlled by RNA cleavage. The data presented here, together with our previous analysis of mRNA and protein synthesis, show that the differential expression of IgM and IgD in normal B lymphocytes is regulated at the transcriptional, translational, and posttranslation levels.