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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / physiology
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Autoantibodies / immunology
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Autoantibodies / metabolism
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B-Lymphocyte Subsets
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B-Lymphocytes / physiology*
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Germinal Center / cytology
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Germinal Center / metabolism
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Homeostasis*
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Humans
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Immunoglobulin Class Switching*
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Immunoglobulins / metabolism
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Integrases / metabolism
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Lymphocyte Activation
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Mice
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Mutation
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PTEN Phosphohydrolase
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Phosphoric Monoester Hydrolases / genetics
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Phosphoric Monoester Hydrolases / metabolism*
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Time Factors
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Viral Proteins / metabolism
Substances
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Autoantibodies
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Immunoglobulins
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Proto-Oncogene Proteins
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Tumor Suppressor Proteins
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Viral Proteins
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Cre recombinase
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Integrases
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase
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PTEN protein, human