Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination.
J Exp Med
; 197(5): 657-67, 2003 Mar 03.
Article
em En
| MEDLINE
| ID: mdl-12615906
ABSTRACT
Pten is a tumor suppressor gene mutated in human cancers. We used the Cre-loxP system to generate a B cell-specific mutation of Pten in mice (bPten(flox/flox)mice). bPten(flox/flox) mice showed elevated numbers of B1a cells and increased serum autoantibodies. Among B2 cells in bPten(flox/flox) spleens, numbers of marginal zone B (MZB) cells were significantly increased while those of follicular B (FOB) cells were correspondingly decreased. Pten-deficient B cells hyperproliferated, were resistant to apoptotic stimuli, and showed enhanced migration. The survival kinase PKB/Akt was highly activated in Pten-deficient splenic B cells. In addition, immunoglobulin class switch recombination was defective and induction of activation-induced cytidine deaminase (AID) was impaired. Thus, Pten plays a role in developmental fate determination of B cells and is an indispensable regulator of B cell homeostasis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Proteínas Serina-Treonina Quinases
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Switching de Imunoglobulina
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Monoéster Fosfórico Hidrolases
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Proteínas Supressoras de Tumor
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Homeostase
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article