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...

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Bibliographic Details
Published in:Nature Immunology 2006-05, Vol.7 (5), p.489-497
Main Authors: Clark, Marcus R, Aifantis, Iannis, Cooper, A Byron, Sawai, Catherine M, Sicinska, Ewa, Powers, Sarah E, Sicinski, Piotr
Format: Article
Language:English
Subjects:
Animals
B cells
B-Lymphocytes - cytology
B-Lymphocytes - immunology
Biomedical and Life Sciences
Biomedicine
Cell differentiation
Cell Differentiation - immunology
Cell Line
Cellular proteins
Cyclin D3
Cyclins - genetics
Cyclins - physiology
Genetic aspects
Hematopoietic stem cells
Immunology
Infectious Diseases
Mice
Mice, Knockout
Physiological aspects
Polymerase Chain Reaction
Properties
Stem cells
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Summary: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 γ-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.
ISSN:1529-2908
1529-2916
1365-2567
DOI:10.1038/ni1324