Cyclin D2 controls B cell progenitor numbers

Cyclin D2 affects B cell proliferation and differentiation in vivo. It is rate‐limiting for B cell receptor (BCR)‐dependent proliferation of B cells, and cyclin D2 −/− mice lack CD5+(B1) B lymphocytes. We show here that the bone marrow (BM) of cyclin D2 −/− mice contains half the numbers of Sca1+B220+ B cell progenitors but normal levels of Sca1+ progenitor cells of other lineages. In addition, clonal analysis of BM from the cyclin D2 −/− and cyclin D2 +/+ mice confirmed that there were fewer B cell progenitors (B220+) in the cyclin D2 −/− mice. In addition, the colonies from cyclin D2 −/− mice were less mature (CD19 lo ) than those from cyclin D2 +/+ mice (CD19 Hi ). The number of mature B2 B cells in vivo is the same in cyclin D2 −/− and cyclin D2 +/+ animals. Lack of cyclin D2 protein may be compensated by cyclin D3, as cyclin‐dependent kinase (cdk)6 coimmunoprecipitates with cyclin D3 but not cyclin D1 from BM mononuclear cells of cyclin D2 −/− mice. It is active, as endogenous retinoblastoma protein is phosphorylated at the cdk6/4‐cyclin D‐specific sites, S 807/811 . We conclude that cyclin D2 is rate‐limiting for the production of B lymphoid progenitor cells whose proliferation does not depend on BCR signaling.