DIFFERENTIAL REGULATION OF MESSENGER-RNAS ENCODING PROTEIN-KINASE-C ISOENZYMES IN ACTIVATED HUMAN B-CELLS

Stimulation of human B cells via HLA class II antigens leads to an inc rease of PKC activity as a consequence of a transcriptional upregulati on of the PKC. Extending previous data, other known B-cell activators, which include anti-IgM, SAC, and TSST1, are shown here to increase th e cytosolic PKC activity significantly. Human B cells express signific ant mRNA levels of the PKC alpha, beta, delta, epsilon, and zeta speci es while the gamma species is consistently absent. The levels of PKC a lpha and epsilon mRNA are increased by exposure to a nonmitogenic anti -IgM antibody in a lymphoblastoid B-cell line while PKC beta and delta mRNA are instead downregulated by this agent. An anti-HLA class II an tibody (D1.12) induced an increase of PKC alpha, beta, and delta mRNA. A time study of PKC mRNA levels in anti-IgM-treated cells showed that the accumulation of the PKC alpha mRNA precedes the increase of PKC e nzymatic activity. Moreover, PKC beta mRNA decreased following treatme nt with SAC while, on the contrary, it increased following TPA, anti-H LA class II (1.35) mAb, or mitogenic anti-IgM treatment. Our results u nderline the complexity of signal transduction via the PKC pathway by revealing that the PKC isoforms are differentially regulated and are i n keeping with the idea that they may have distinct physiologic roles in human B cells.