Cyclin D2 controls B cell progenitor numbers

A Mohamedali, I Soeiro, N C Lea, J Glassford, L Banerji, G J Mufti, E W F Lam, N S B Thomas

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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 (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.
Original languageEnglish
Pages (from-to)1139 - 1143
Number of pages5
JournalJournal of Leukocyte Biology
Volume74
Issue number6
DOIs
Publication statusPublished - Dec 2003

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