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

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

Research output: Contribution to journalArticle

168 Citations (Scopus)

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 (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.

Original languageEnglish (US)
Pages (from-to)657-667
Number of pages11
JournalJournal of Experimental Medicine
Volume197
Issue number5
DOIs
StatePublished - Mar 3 2003

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Immunoglobulin Isotypes
Genetic Recombination
Homeostasis
B-Lymphocytes
Tumor Suppressor Genes
Autoantibodies
Phosphotransferases
Spleen
Cell Count
Mutation
Serum
Neoplasms

Keywords

  • Activation-induced cytidine deaminase
  • Class switch recombination
  • Marginal zone B cells
  • Mutation
  • PTEN

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Suzuki, A., Kaisho, T., Ohishi, M., Tsukio-Yamaguchi, M., Tsubata, T., Koni, P. A., ... Nakano, T. (2003). Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination. Journal of Experimental Medicine, 197(5), 657-667. https://doi.org/10.1084/jem.20021101

Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination. / Suzuki, Akira; Kaisho, Tsuneyasu; Ohishi, Minako; Tsukio-Yamaguchi, Manae; Tsubata, Takeshi; Koni, Pandelakis A.; Sasaki, Takehiko; Mak, Tak Wah; Nakano, Toru.

In: Journal of Experimental Medicine, Vol. 197, No. 5, 03.03.2003, p. 657-667.

Research output: Contribution to journalArticle

Suzuki, A, Kaisho, T, Ohishi, M, Tsukio-Yamaguchi, M, Tsubata, T, Koni, PA, Sasaki, T, Mak, TW & Nakano, T 2003, 'Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination', Journal of Experimental Medicine, vol. 197, no. 5, pp. 657-667. https://doi.org/10.1084/jem.20021101
Suzuki A, Kaisho T, Ohishi M, Tsukio-Yamaguchi M, Tsubata T, Koni PA et al. Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination. Journal of Experimental Medicine. 2003 Mar 3;197(5):657-667. https://doi.org/10.1084/jem.20021101
Suzuki, Akira ; Kaisho, Tsuneyasu ; Ohishi, Minako ; Tsukio-Yamaguchi, Manae ; Tsubata, Takeshi ; Koni, Pandelakis A. ; Sasaki, Takehiko ; Mak, Tak Wah ; Nakano, Toru. / Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination. In: Journal of Experimental Medicine. 2003 ; Vol. 197, No. 5. pp. 657-667.
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