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Phosphatidylinositol 3-kinase improves the efficiency of positive selection

Barbee, Susannah D. and Alberola-Ila, José (2006) Phosphatidylinositol 3-kinase improves the efficiency of positive selection. International Immunology, 18 (6). pp. 921-930. ISSN 0953-8178. doi:10.1093/intimm/dxl027.

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We have generated transgenic mice expressing the amino-terminal fragment of the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110(ABD)) in thymocytes. Expression of P110(ABD) 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 p110(ABD) 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.

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Additional Information:© The Japanese Society for Immunology 2006. Received 9 November 2005, accepted 21 March 2006. We thank G. Hernández-Hoyos and S. Kovats for critically reading the manuscript, K. Forbush for the transgenic injections; C. Wang for technical assistance and B. Kennedy and the personnel at the Caltech Transgenic Mouse Facility for mouse husbandry. Supported by the National Institutes of Health (NIH) (AI45072 to J.A.I.). The authors have no conflicting financial interests.
Subject Keywords:development, PI3K, positive selection, T cell, thymus
Issue or Number:6
Record Number:CaltechAUTHORS:BARintimm06
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:4025
Deposited By: Lindsay Cleary
Deposited On:25 Jul 2006
Last Modified:08 Nov 2021 20:14

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