Critical Roles of Pten in B Cell Homeostasis and Immunoglobulin Class Switch Recombination-Reference-Cited by-同舟云学术

Critical Roles of Pten in B Cell Homeostasis and Immunoglobulin Class Switch Recombination

Published:2003-03-03 Issue:5 Volume:197 Page:657-667
ISSN:1540-9538
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Suzuki Akira¹²³,Kaisho Tsuneyasu⁴⁵,Ohishi Minako¹,Tsukio-Yamaguchi Manae¹,Tsubata Takeshi⁶,Koni Pandelakis A.⁷,Sasaki Takehiko⁸³,Mak Tak Wah³,Nakano Toru¹

Affiliation:

1. Department of Molecular Cell Biology, Research Institute for Microbial Disease, Osaka University, Osaka 565-0871, Japan

2. Department of Biochemistry, Akita University School of Medicine, Akita 010-8543, Japan

3. Advanced Medical Discovery Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada

4. Department of Host Defense, Research Institute for Microbial Disease, Osaka University, Osaka 565-0871, Japan

5. RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan

6. Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan

7. Molecular Immunology Program, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912

8. Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Link

http://rupress.org/jem/article-pdf/197/5/657/1143994/jem1975657.pdf

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