Activation and proliferation signals in mouse B cells II. Evidence for activation (G₀ to G₁) signals differing in sensitivity to cyclosporine

We have previously shown that cyclosporine (CS) selectively inhibits polyclonal activation of B cells by anti-Ig antibodies but not by lipopolysaccharide (LPS). Here we extend these results using a two-stage B cell culture system in which cells from either CBA/N or normal mice are activated to enter G1 by anti-Ig, and are then stimulated to proliferate by LPS. In this system CS blocks an event that occurs within 4 h after initial activation, i.e. prevents entry of B cells into G1. Phorbol myristic acetate also induces some CBA/N B cells to enter G1. However, activation of B cells by this agent is resistant to inhibition by CS. These data suggest that there are two biochemically distinct mechanisms for driving resting B cells into G1. A hypothesis to explain these results is presented.