Suppression of phosphatidylinositol 3,4,5-trisphosphate production is a key determinant of B cell anergy.
Immunity
; 31(5): 749-60, 2009 Nov 20.
Article
em En
| MEDLINE
| ID: mdl-19896393
ABSTRACT
Anergy is a critical physiologic mechanism to sensor self-reactive B cells. However, a biochemical understanding of how anergy is achieved and maintained is lacking. Herein, we investigated the role of the phosphoinositide 3-kinase (PI3K) lipid product PI(3,4,5)P(3) in B cell anergy. We found reduced generation of PI(3,4,5)P(3) in anergic B cells, which was attributable to reduced phosphorylation of the PI3K membrane adaptor CD19, as well as increased expression of the inositol phosphatase PTEN. Sustained production of PI(3,4,5)P(3) in B cells, achieved through conditional deletion of Pten, resulted in failed tolerance induction and abundant autoantibody production. In contrast to wild-type immature B cells, B cell receptor engagement of PTEN-deficient immature B cells resulted in activation and proliferation, indicating a central defect in early B cell responsiveness. These findings establish repression of the PI3K signaling pathway as a necessary condition to avert the generation, activation, and persistence of self-reactive B cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Fosfatos de Fosfatidilinositol
/
Anergia Clonal
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article