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

180 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Suzuki, A., Kaisho, T., Ohishi, M., Tsukio-Yamaguchi, M., Tsubata, T., Koni, P. A., Sasaki, T., Mak, T. W., & 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