Using a subtractlve strategy, we have cloned an activation-related gene from a human B cell cDNA library. Sequence analysis revealed that this gene was identical to H12.3, a gene belonging to an expanding family of guanlne nucleotlde-blndlng protein β subunlts. The expression of H12.3 was induclble in the late phase of mltogen-stlmulated T and B cells. In T cells, IL-2 and IL-4 by themselves had no direct effect on the expression of H12.3, but they could augment the level of steady-state H12.3 mRNA stimulated by phytohemagglutlnln. On the other hand, IFN-γ and IL-6 had no obvious effect on the expression in B cells with or without Staphytococcus aureus Cowan l-stlmulatlon. Cyclosporin A, a strong immunosuppressant, Inhibited the mltogen-stlmulated expression of H12.3, but rapamycin, another such agent, did not. In synchronized Jurkat cells, the expression of H12.3 had no cell cycle-dependent decrease in S and G2/M phase, while cyclin E, which controls the progression of the cell cycle un late G1 phase, did show a periodic expression pattern. The results suggest that H12.3 might be involved in regulation of lymphocyte activation.