CELL CYCLE-SPECIFIC INDUCTION OF CDK2 EXPRESSION IN B-LYMPHOCYTES FOLLOWING ANTIGEN RECEPTOR CROSS-LINKING

The ligation of membrane Ig (mig) on quiescent primary B lymphocytes b y mitogenic concentrations of anti-IgM antibodies leads to cell cycle progression. The level of cyclin-dependent kinase 2 (Cdk2) expression was found to be restricted to specific phases of the cell cycle in pri mary cultures of murine B lymphocytes. Resting G(0) phase, G(1) phase, or B cells arrested near the G(1)/S boundary by hydroxyurea contained no detectable Cdk2 protein or associated histone H1 kinase activity. In contrast, B cell entry into S phase was accompanied by an induction in the expression of cellular Cdk2 as judged by immunoblotting of B c ell lysates with anti-Cdk2 antibodies. Concomitant with S phase entry was the detection of anti-Cdk2-specific immunoprecipitable histone H1 kinase activity. Further analysis revealed that the amount of cyclin A protein also oscillated during cell cycle, appearing initially in G(1 ) phase B cells. Cyclin A was found to be associated with Cdk2 in B ce lls during S phase progression. These results indicate that cross-link ing of mig on primary B lymphocytes results in the ''downstream'' cata lytic activation of Cdk2. The timing of Cdk2 expression and its associ ation with cyclin A suggests that Cdk2 may not be involved in the deci sion to enter S phase, but rather may provide a role in the maintenanc e of S phase progression or in preparing B cells to enter M phase.