A unique function for cyclin D3 in early B cell development

Abstract
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.

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