Cyclin D2controls B cell progenitor numbers

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Abstract
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 (CD19lo) than those from cyclin D2+/+ mice (CD19Hi). 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, S807/811. We conclude that cyclin D2 is rate-limiting for the production of B lymphoid progenitor cells whose proliferation does not depend on BCR signaling.
Funding Information
  • Charles Wolfson Charitable Trust
  • Leukaemia Research Fund
  • Cancer Research–UK
  • Fundação para a Ciência e a Tecnologia, Portugal
  • A University of London Trust Postgraduate Studentship