Cyclin D2 controls B cell progenitor numbers

• Published in: Journal of leukocyte biology Vol. 74; no. 6; pp. 1139 - 1143
• Main Authors: Mohamedali, Azim, Soeiro, Inês, Lea, Nicholas C., Glassford, Janet, Banerji, Lolita, Mufti, Ghulam J., Lam, Eric W.‐F., Thomas, N. Shaun B.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.12.2003
• Subjects: Animals; Antigens, CD19 - metabolism; Antigens, Differentiation - metabolism; B lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; Blotting, Western; bone marrow; Bone Marrow - metabolism; CD5 Antigens - analysis; CD5 Antigens - metabolism; Cell Count; Cells, Cultured; cellular proliferation; Colony-Forming Units Assay; Cyclin D2; Cyclin D3; Cyclins - metabolism; Cyclins - physiology; Hematopoietic Stem Cells - cytology; Mice; Mice, Inbred C57BL; Mice, Knockout; mouse; Oncogene Proteins - metabolism; Phosphorylation; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcr; Retinoblastoma Protein - metabolism; Sca1; Signal Transduction
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0803363

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.