Molecular events in B lymphocyte activation: consequences of signals transduced through MHC class II molecules.

Evidence is presented to demonstrate that murine B lymphocytes receive growth stimulatory signals from their surface class II molecules. Monoclonal anti-Ia antibodies enhanced anti-mu-induced B cell proliferative response. The signals through surface immunoglobulin (Ig) and Ia appeared to act sequentially since preexposure to anti-mu was required to observe anti-Ia-induced increase in B cell proliferation. Anti-Ia antibodies did not increase the number of B cells entering the G1 phase of cell cycle but always enhanced transition from G1 into the S phase in response to stimulation with anti-mu. Analysis of early gene expression revealed that signaling through class II molecules led to an increase in anti-mu-induced expression of c-myc, a proto-oncogene, and of ornithine decarboxylase, a key enzyme in polyamine biosynthesis that has been shown to be intimately related to increased cell proliferation.