Cyclin D2 controls B cell progenitor numbers.
A Z Mohamedali, Inês Soeiro, Nicholas Lea, Janet Glassford, Lolita Banerji, Ghulam Mufti, Eric W.‐F. Lam, Shaun A. Thomas
Abstract
A Z Mohamedali, Inês Soeiro, Nicholas Lea, Janet Glassford, Lolita Banerji, Ghulam Mufti, Eric W.‐F. Lam, Shaun A. Thomas
Abstract
Cyclin D2 activates the cyclin dependent kinases cdk6 and cdk4. Recently, we identified a commitment point (CP) that regulates transition into the cell cycle from a quiescent state (Lea et al., 2003 Mol Cell Biol. 23:2351-61). Activation of cdk6/4 by cyclin D2 is rate limiting for transition through the G0fwdarwG1 CP. Cyclin D2 affects B cell proliferation and differentiation in vivo and we have previously shown that it is rate limiting for B cell receptor (BCR)-dependent proliferation of B cells. In addition, cyclin D2-/- mice lack CD5+(B1)-B-lymphocytes (Solvason et al., 2000 Int. Immunol. 12:631-8). Furthermore, the number of mature B2-B cells in vivo is the same in cyclin D2-/- and cyclin D2+/+ animals. We investigated whether cyclin D2 has a role in regulating B-lymphoid progenitor cells that do not depend on BCR-signalling to stimulate proliferation. We show here that the bone marrow of cyclin D2-/- mice contain half the numbers of Sca1+B220+B cell progenitors but normal levels of Sca1+ progenitor cells of other lineages (p
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Cyclin D2 activates the cyclin dependent kinases cdk6 and cdk4. Recently, we identified a commitment point (CP) that regulates transition into the cell cycle from a quiescent state (Lea et al., 2003 Mol Cell Biol. 23:2351-61). Activation of cdk6/4 by cyclin D2 is rate limiting for transition through the G0fwdarwG1 CP. Cyclin D2 affects B cell proliferation and differentiation in vivo and we have previously shown that it is rate limiting for B cell receptor (BCR)-dependent proliferation of B cells. In addition, cyclin D2-/- mice lack CD5+(B1)-B-lymphocytes (Solvason et al., 2000 Int. Immunol. 12:631-8). Furthermore, the number of mature B2-B cells in vivo is the same in cyclin D2-/- and cyclin D2+/+ animals. We investigated whether cyclin D2 has a role in regulating B-lymphoid progenitor cells that do not depend on BCR-signalling to stimulate proliferation. We show here that the bone marrow of cyclin D2-/- mice contain half the numbers of Sca1+B220+B cell progenitors but normal levels of Sca1+ progenitor cells of other lineages (p
Key concepts: Cyclin D2, Cyclin D, Cyclin A2, Cyclin B, Cyclin A, Cyclin D1, Cyclin D3, Cyclin E