A unique function for cyclin D3 in early B cell development

被引:101
作者
Cooper, AB
Sawai, CM
Sicinska, E
Powers, SE
Sicinski, P
Clark, MR [1 ]
Aifantis, I
机构
[1] Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA
[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA
关键词
D O I
10.1038/ni1324
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:489 / 497
页数:9
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