Stimulation of human B cells via HLA class II antigens leads to an increase of PKC activity as a consequence of a transcriptional upregulation of the PKC. Extending previous data, other known B-cell activators, which include anti-IgM, SAC, and TSST1, are shown here to increase the cytosolic PKC activity significantly. Human B cells express significant mRNA levels of the PKC alpha, beta, delta, epsilon, and zeta species while the gamma species is consistently absent. The levels of PKC alpha 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 antibody (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 enzymatic activity. Moreover, PKC beta mRNA decreased following treatment with SAC while, on the contrary, it increased following TPA, anti-HLA class II (1.35) mAb, or mitogenic anti-IgM treatment. Our results underline the complexity of signal transduction via the PKC pathway by revealing that the PKC isoforms are differentially regulated and are in keeping with the idea that they may have distinct physiologic roles in human B cells.