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

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    Authors
    Suzuki, Akira
    Kaisho, Tsuneyasu
    Ohishi, Minako
    Tsukio-Yamaguchi, Manae
    Tsubata, Takeshi
    Koni, Pandelakis A.
    Sasaki, Takehiko
    Mak, Tak Wah
    Nakano, Toru
    Issue Date
    2003-03-3
    URI
    http://hdl.handle.net/10675.2/555
    
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    Abstract
    Pten is a tumor suppressor gene mutated in human cancers. We used the Cre-loxP system to generate a B cellâ specific mutation of Pten in mice (bPtenflox/floxmice). bPtenflox/flox mice showed elevated numbers of B1a cells and increased serum autoantibodies. Among B2 cells in bPtenflox/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.
    Citation
    J Exp Med. 2003 Mar 3; 197(5):657-667
    ae974a485f413a2113503eed53cd6c53
    10.1084/jem.20021101
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