Critical Roles of Pten in B Cell Homeostasis and Immunoglobulin Class Switch Recombination
Koni, Pandelakis A.
Mak, Tak Wah
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AbstractPten 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.
CitationJ Exp Med. 2003 Mar 3; 197(5):657-667
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