TY - JOUR
T1 - Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination
AU - Suzuki, Akira
AU - Kaisho, Tsuneyasu
AU - Ohishi, Minako
AU - Tsukio-Yamaguchi, Manae
AU - Tsubata, Takeshi
AU - Koni, Pandelakis A.
AU - Sasaki, Takehiko
AU - Mak, Tak Wah
AU - Nakano, Toru
PY - 2003/3/3
Y1 - 2003/3/3
N2 - 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 (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.
AB - 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 (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.
KW - Activation-induced cytidine deaminase
KW - Class switch recombination
KW - Marginal zone B cells
KW - Mutation
KW - PTEN
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U2 - 10.1084/jem.20021101
DO - 10.1084/jem.20021101
M3 - Article
C2 - 12615906
AN - SCOPUS:0037416216
SN - 0022-1007
VL - 197
SP - 657
EP - 667
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -
