A unique function for cyclin D3 in early B cell development.
During hematopoiesis, stem cell proliferation is dependent on expression of the D-type cyclins. However, little is known about how each cyclin D contributes to the development of specific hematopoietic lineages. Here, analysis of Ccnd1(-/-), Ccnd2(-/-), Ccnd3(-/-) and Ccnd2(-/-)Ccnd3(-/-) mice showed that cyclin D3 was uniquely required for the development of pre-B cells. Transcription of Ccnd3 was dependent on expression of the common gamma-chain. In contrast, expression of the pre-B cell receptor and activation of 'downstream' signaling pathways prevented proteasome-mediated degradation of cyclin D3. Cyclin D3 has a key function in B cell development by integrating cytokine and pre-B cell receptor-dependent signals to expand the pool of pre-B cells that have successfully rearranged immunoglobulin heavy chain.
Cooper
A Byron
AB
Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois 60637, USA.
Sawai
Catherine M
CM
Sicinska
Ewa
E
Powers
Sarah E
SE
Sicinski
Piotr
P
Clark
Marcus R
MR
Aifantis
Iannis
I
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction
C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins