Critical Roles of Pten in B Cell Homeostasis and Immunoglobulin Class Switch Recombination
Authors
Suzuki, AkiraKaisho, Tsuneyasu
Ohishi, Minako
Tsukio-Yamaguchi, Manae
Tsubata, Takeshi
Koni, Pandelakis A.
Sasaki, Takehiko
Mak, Tak Wah
Nakano, Toru
Issue Date
2003-03-3
Metadata
Show full item recordAbstract
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):657-667ae974a485f413a2113503eed53cd6c53
10.1084/jem.20021101
Scopus Count
Related articles
- Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation.
- Authors: Suzuki A, Itami S, Ohishi M, Hamada K, Inoue T, Komazawa N, Senoo H, Sasaki T, Takeda J, Manabe M, Mak TW, Nakano T
- Issue date: 2003 Feb 1
- T cell-specific loss of Pten leads to defects in central and peripheral tolerance.
- Authors: Suzuki A, Yamaguchi MT, Ohteki T, Sasaki T, Kaisho T, Kimura Y, Yoshida R, Wakeham A, Higuchi T, Fukumoto M, Tsubata T, Ohashi PS, Koyasu S, Penninger JM, Nakano T, Mak TW
- Issue date: 2001 May
- Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas.
- Authors: Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J, Mizuno K, Hasegawa G, Kishimoto H, Iizuka M, Naito M, Enomoto K, Watanabe S, Mak TW, Nakano T
- Issue date: 2004 Jun
- Functional analysis of the tumour suppressor gene PTEN in murine B cells and keratinocytes.
- Authors: Suzuki A, Sasaki T, Mak TW, Nakano T
- Issue date: 2004 Apr
- Akt regulates COX-2 mRNA and protein expression in mutated-PTEN human endometrial cancer cells.
- Authors: St-Germain ME, Gagnon V, Mathieu I, Parent S, Asselin E
- Issue date: 2004 May