TPA-induced differentiation of chronic lymphocytic leukemia cells: studies on mu-chain expression.

The regulation of IgM synthesis and secretion was studied in chronic lymphocytic leukemia cells, with a phenotype roughly similar to peripheral resting B cells, during phorbol ester (12-O-tetradecanoylphorbol-13-acetate)-induced differentiation. TPA treatment caused a 20 times increase in total RNA synthesis and 20 to 50 times increase in the protein synthesis as compared to control cells. Morphologically, 70-90% of the cells reached the lympho- or plasmablast stage of differentiation. In control culture cells, approximately equal amounts of mRNA coding for secretory (s) and membrane (m) mu-chains were found. The micron message was translated as surface IgM expression was detected. A posttranscriptional regulation of microsecond synthesis appears to exist, since only low amounts of cytoplasmic mu-chains were detected by immunoprecipitation and SDS-PAGE, and no secretion of pentameric IgM was detected as measured by an RIA. TPA induction caused a relative increase in the microseconds to microns mRNA ratio, demonstrating differentiation associated control mechanisms operating at the level of mRNA processing. The high levels of cytoplasmic microsecond-chain precursor and the efficient secretion of pentameric IgM in TPA-induced chronic lymphocytic leukemia cells indicated the presence also of posttranscriptional controls.