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Related Experiment Videos

A unique function for cyclin D3 in early B cell development.

A Byron Cooper1, Catherine M Sawai, Ewa Sicinska

  • 1Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, Illinois 60637, USA.

Nature Immunology
|April 4, 2006
PubMed
Summary
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Cyclin D3 is essential for pre-B cell development during hematopoiesis. It integrates signals to expand the B cell pool after immunoglobulin heavy chain rearrangement.

Area of Science:

  • Immunology
  • Cell Biology
  • Hematopoiesis

Background:

  • D-type cyclins regulate stem cell proliferation during hematopoiesis.
  • The specific roles of individual cyclin D proteins in hematopoietic lineage development are not well understood.

Purpose of the Study:

  • To investigate the distinct functions of cyclin D1, D2, and D3 in hematopoietic lineage development.
  • To elucidate the regulatory mechanisms controlling cyclin D3 expression and function in B cell development.

Main Methods:

  • Analysis of knockout mouse models (Ccnd1-/-, Ccnd2-/-, Ccnd3-/-, Ccnd2-/-Ccnd3-/-).
  • Investigated the dependence of Ccnd3 transcription on the common gamma-chain.
  • Examined the regulation of cyclin D3 stability via pre-B cell receptor signaling and proteasomal degradation pathways.

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Main Results:

  • Cyclin D3 was found to be uniquely required for the development of pre-B cells.
  • Ccnd3 transcription is dependent on the common gamma-chain.
  • Pre-B cell receptor signaling and downstream pathways inhibit proteasome-mediated degradation of cyclin D3, stabilizing the protein.

Conclusions:

  • Cyclin D3 plays a critical role in B cell development by integrating cytokine and pre-B cell receptor signals.
  • This integration by cyclin D3 expands the pre-B cell population that has successfully rearranged the immunoglobulin heavy chain.