Details

Autor(en) / Beteiligte

• Suzuki, Akira
• Kaisho, Tsuneyasu
• Ohishi, Minako
• Tsukio-Yamaguchi, Manae
• Tsubata, Takeshi
• Koni, Pandelakis A
• Sasaki, Takehiko
• Mak, Tak Wah
• Nakano, Toru

Titel

Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination

Ist Teil von

• The Journal of experimental medicine, 2003-03, Vol.197 (5), p.657-667

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2003

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.