| First Author | Cato MH | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 1 | Pages | 127-37 |
| PubMed ID | 20956554 | Mgi Jnum | J:169426 |
| Mgi Id | MGI:4940958 | Doi | 10.1128/MCB.00650-10 |
| Citation | Cato MH, et al. (2011) Cyclin D3 is selectively required for proliferative expansion of germinal center B cells. Mol Cell Biol 31(1):127-37 |
| abstractText | 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. |
