期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 197, 期 5, 页码 657-667出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20021101
关键词
PTEN; mutation; marginal zone B cells; class switch recombination; activation-induced cytidine deaminase
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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