Critical Roles of Pten in B Cell Homeostasis and Immunoglobulin Class Switch Recombination

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) sp...

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Detalles Bibliográficos
Autores principales: Suzuki, Akira, Kaisho, Tsuneyasu, Ohishi, Minako, Tsukio-Yamaguchi, Manae, Tsubata, Takeshi, Koni, Pandelakis A., Sasaki, Takehiko, Mak, Tak Wah, Nakano, Toru
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193827/
https://www.ncbi.nlm.nih.gov/pubmed/12615906
http://dx.doi.org/10.1084/jem.20021101
Descripción
Sumario: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.

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