Your browser doesn't support javascript.
loading
Cyclin D3 is selectively required for proliferative expansion of germinal center B cells.
Cato, Matthew H; Chintalapati, Suresh K; Yau, Irene W; Omori, Sidne A; Rickert, Robert C.
Afiliação
  • Cato MH; Program on Inflammatory Disease Research, Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
Mol Cell Biol ; 31(1): 127-37, 2011 Jan.
Article em En | MEDLINE | ID: mdl-20956554
ABSTRACT
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Linfócitos B / Centro Germinativo / Ciclina D3 Limite: Animals Idioma: En Revista: Mol Cell Biol Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Linfócitos B / Centro Germinativo / Ciclina D3 Limite: Animals Idioma: En Revista: Mol Cell Biol Ano de publicação: 2011 Tipo de documento: Article