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International Immunology Advance Access published online on April 24, 2006
International Immunology, doi:10.1093/intimm/dxl027
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received November 9, 2005
Accepted March 21, 2006

Article

Phosphatidylinositol 3-kinase improves the efficiency of positive selection

Susannah D. Barbee 1 and José Alberola-Ila 2 *

1 Division of Biology, California Institute of Technology, 1200 E. California Boulevard, Mail code 147-75, Pasadena, CA 91125, USA; Present address: Peter Gorer Department of Immunobiology, 2nd Floor, New Guy's House, GKT School of Medicine, King's College London, London, SE1 9RT, UK
2 Division of Biology, California Institute of Technology, 1200 E. California Boulevard, Mail code 147-75, Pasadena, CA 91125, USA; Present address: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, MS# 36, Oklahoma City, OK 73104, USA

* To whom correspondence should be addressed.
José Alberola-Ila, E-mail: jose-alberola-ila{at}omrf.ouhsc.edu


  Abstract

We have generated transgenic mice expressing the amino-terminal fragment of the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110ABD) in thymocytes. Expression of p110ABD results in constitutive activation of PI3K and in significant increases in the numbers of mature, single-positive thymocytes. We previously reported that the increase in mature cells was in part due to a defect in thymic emigration. In this study we identify another component to this phenotype. Expression of p110ABD results in an enhancement of positive selection, without alterations in thymocyte lifespan or negative selection. Since PI3K can affect activation of Btk, which in turn potentiates calcium fluxes, during B cell development, our results suggest that PI3K could play a role in the regulation of Itk kinases in T cells, and that both cell types share a common signaling network to modulate calcium responses downstream of their antigen receptor.

Keywords: development; PI3K; positive selection; T cell; thymus.
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