Regulation of immunoglobulin transcription rates and mRNA processing in proliferating normal B lymphocytes by activators of protein kinase C

Abstract

Immunoglobulin gene expression in normal splenic B lymphocytes stimulated with lipopolysaccharide was selectively down-regulated by anti-IgM antibodies and a protein-kinase C-activating phorbol ester, phorbol 12,13-dibutyrate. This control was concomitant with a decreased rate of transcription of the IgM gene while "polymerase pausing" was induced in the IgD gene. The suppression was resistant to treatment with cycloheximide, indicating that it was not caused by a labile repressor protein. The down-regulation of immunoglobulin gene expression affected only the secretory form of immunoglobulin, while the mRNA levels for the membrane-bound form of immunoglobulin remained unaltered. We conclude that the mechanisms controlling immunoglobulin gene expression in untransformed B lymphocytes differ from those operating in tumors derived from the same cell lineage.