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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0803363


Received for publication August 1, 2003.
Revised August 22, 2003.
Accepted for publication September 9, 2003.


Article

Cyclin D2 controls B cell progenitor numbers

Azim Mohamedali *, Inês Soeiro {dagger}, Nicholas C. Lea *, Janet Glassford {dagger}, Lolita Banerji {dagger}, Ghulam J. Mufti *, Eric W.-F. Lam {dagger}, and N. Shaun B. Thomas *@

*Department of Haematological Medicine, Leukaemia Sciences, Guy’s, King’s, St. Thomas’ School of Medicine, Rayne Institute, London, United Kingdom; and {dagger}Cancer Research-UK Labs and Section of Cancer Cell Biology, Imperial College School of Medicine at Hammersmith Hospital, London, United Kingdom

@ To whom correspondence should be addressed. E-mail: nicholas.s.thomas{at}kcl.ac.uk.


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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.

Key Words: mouse • bone marrow • Sca1+ • B lymphocytes • cellular proliferation




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