Regulation of expression of immunoglobulins M and D in murine B cells.

Immunoglobulins M (IgM) and D (IgD) are expressed in a coordinantly regulated and differentiation-dependent fashion on the surface of B lymphocytes. We have studied the role of DNA configuration of their linked constant region genes C mu and C delta, as well as their transcription and posttranscriptional processing, in the regulation of these changes. After rearrangement of variable region segments, IgD can be singularly expressed in plasmacytoma cells by a DNA deletion of the C mu gene that is mediated by illegitimate recombination. However, IgM and IgD are usually expressed jointly without further DNA rearrangement downstream of VDJ. In pre-B cells, C delta apparently is not transcribed before light-chain expression. However, in early neonates (2 days old), C delta is transcribed at approximately one-third the level of C mu even though IgD is not detectable on the cell surface. This same ratio of transcription is preserved in older neonates (12 days old), which express only modest quantities of IgD, and in mature resting B cells, which express far higher densities of cell surface IgD than IgM. On activation by mitogens, transcription of C mu is preferentially enhanced, but it is surprising that C delta transcription remains at the baseline level even though cytoplasmic delta mRNA is virtually undetectable. The apparent discrepancy in transcription and ultimate expression can be explained by further modifications of both the RNA and polypeptide chains. Collectively, our data show that the differential expression of IgM and IgD is regulated by complex mechanisms at several levels.