Da. Tanguay et Tc. Chiles, CELL CYCLE-SPECIFIC INDUCTION OF CDK2 EXPRESSION IN B-LYMPHOCYTES FOLLOWING ANTIGEN RECEPTOR CROSS-LINKING, Molecular immunology, 31(9), 1994, pp. 643-649
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.