Regulation of immunoglobulin gene expression in trans by phorbol esters.

Lipopolysaccharide-stimulated B cell cultures treated with phorbol-12,13-dibutyrate have been shown to down-regulate their steady state levels of microseconds RNA while the microns RNA remained constant. In contrast, the steady state levels of delta RNA was up-regulated by the same treatment. By using mice transgenic for a rearranged mu or delta gene, it could be shown that the down-regulatory effect acts in trans on a defined DNA stretch and is independent of isotype. Thus, the positive effect on endogenous delta RNA steady-state levels must be regulated at the level of RNA processing. In addition, a DNA construct containing 1.5 kb of a kappa promoter 5' of, and an IgH enhancer 3' of, a chloramphenicol acetyl transferase reporter gene could be down-regulated in trans by anti-mu- or phorbol-12,13-dibutyrate treatment, showing that transcriptional control of Ig promoter elements can readily be observed in non-transformed B lymphocytes.