Cutting edge: Differential signaling requirements for activation of assembled cyclin D3-cdk4 complexes in B-1 and B-2 lymphocyte subsets

B-1 lymphocytes represent a distinct B cell subset with unusual mitogenic r esponses. PMA alone promotes proliferation in B-1 cells, but not in splenic B-2 cells. Although cyclin D2-cyclin-dependent kinase 4 (cdk4) complexes m ediate early retinoblastoma gene product (pRb) phosphorylation in B-1 cells , the transient nature of their accumulation cannot account for the continu ed increase in pRb phosphorylation, which is maximal at 24 h. We show herei n that PMA promotes the accumulation of functional cyclin D3-cdk4 complexes in B-1 cells following loss of cyclin D2. PMA also induces accumulation of cyclin D3-cdk4 complexes in B-2 cells; however, these complexes do not pho sphorylate pRb. Thus, PMA is sufficient to induce synthesis and assembly of cyclin D3-cdk4 complexes in B-1 and B-2 cells; however, PMA triggers cycli n D3-cdk4 activation only in B-1 cells. These results reveal a novel regula tory step that controls activation of cyclin D3-cdk4 complexes whose functi on segregates differentially in B cell subsets.