Transcriptional control of mu- and kappa-gene expression in resting and bacterial lipopolysaccharide-activated normal B cells.

When murine resting B cells are polyclonally stimulated by bacterial lipopolysaccharide (LPS) in vitro for a short period of 4 days, they are activated to DNA synthesis and cell division, and they also differentiate to immunoglobulin (Ig)-secreting plasma cells. These two events are accompanied with several qualitative changes at the Ig mRNA level: the disappearance of delta mRNA after stimulation, the switch from membrane to secretory form of mu-mRNA, and the late appearance of IgM joining chain (J-chain) mRNA. There is also a quantitative increase of Ig-gene expression at the level of: Ig gene transcription, mu-, kappa- and J-chain mRNA accumulation, and Ig translation and secretion. A comparison of Ig transcription rates before and in the course of LPS stimulation, as determined by in vitro transcriptional run-on assays, has shown that there is a large increase of the RNA polymerase density on both mu- and kappa-loci (30-60-fold), which is quantitatively comparable with the accumulation of both mu- and kappa-mRNAs at the steady state mRNA level. These data therefore suggest that former results obtained with tumor cells regarding post-transcriptional control of Ig gene expression do not reflect the physiological behavior of normal B cells with respect to the molecular events of B cell triggering. We also propose that additional molecular events such as RNA processing and the transcriptional activation of J-chain gene might be essential for controlling the maximal transcriptional rate across the Ig loci.