Cyclin D3 is selectively required for proliferative expansion of germinal center B cells
Autor: | Irene W. Yau, Sidne A. Omori, Robert C. Rickert, Matthew H. Cato, Suresh K. Chintalapati |
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Rok vydání: | 2010 |
Předmět: |
Cellular differentiation
Gene Expression Biology Immunoglobulin D Glycogen Synthase Kinase 3 Mice Cyclin D2 GSK-3 Animals Cyclin D3 Molecular Biology Cell Proliferation DNA Primers Mice Knockout B-Lymphocytes Base Sequence Kinase Models Immunological Germinal center Cell Differentiation Cell Biology T-Lymphocytes Helper-Inducer Articles Germinal Center Cancer research biology.protein Immunization Signal transduction Signal Transduction |
Zdroj: | Molecular and cellular biology. 31(1) |
ISSN: | 1098-5549 |
Popis: | The generation of robust T-cell-dependent humoral immune responses requires the formation and expansion of germinal center structures within the follicular regions of the secondary lymphoid tissues. B-cell proliferation in the germinal center drives ongoing antigen-dependent selection and the generation of high-affinity class-switched plasma and memory B cells. However, the mechanisms regulating B-cell proliferation within this microenvironment are largely unknown. Here, we report that cyclin D3 is uniquely required for germinal center progression. Ccnd3(-/-) mice exhibit a B-cell-intrinsic defect in germinal center maturation and fail to generate an affinity-matured IgG response. We determined that the defect resulted from failed proliferative expansion of GL7(+) IgD(-) PNA(+) B cells. Mechanistically, sustained expression of cyclin D3 was found to be regulated at the level of protein stability and controlled by glycogen synthase kinase 3 in a cyclic AMP-protein kinase A-dependent manner. The specific defect in proliferative expansion of GL7(+) IgD(-) PNA(+) B cells in Ccnd3(-/-) mice defines an underappreciated step in germinal center progression and solidifies a role for cyclin D3 in the immune response, and as a potential therapeutic target for germinal center-derived B-cell malignancies. |
Databáze: | OpenAIRE |
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