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International Immunology Advance Access published online on November 1, 2004
International Immunology, doi:10.1093/intimm/dxh180
© 2004 by The Japanese Society for Immunology
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Received June 25, 2004
Accepted September 28, 2004

Article

Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85{alpha}

Amber C. Donahue 1, Kristen L. Hess 1, Kwan L. Ng 1, and David A. Fruman 1*

1 Center for Immunology and Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA

* To whom correspondence should be addressed.
David A. Fruman, E-mail: dfruman{at}uci.edu


  Abstract

The signaling enzyme phosphoinositide 3-kinase (PI3K) is activated following B cell receptor (BCR) engagement and by many other receptors on B lymphocytes. Mice lacking p85{alpha}, the predominant PI3K regulatory isoform, exhibit defects in B cell development and activation that are grossly similar to those found in mice lacking Bruton's tyrosine kinase (Btk) and other critical signaling molecules. However, a detailed analysis of splenic B cell subsets in p85{alpha}-deficient mice has not been reported. Here we show that these mice are deficient in four major B cell subsets: transitional-1, transitional-2, follicular and marginal zone. These defects are distinct from those observed in Xid mice that express a mutant Btk unable to interact with PI3K lipid products. Moreover, mice with both genetic lesions exhibit even greater impairment in B cell development. Finally, we show that transgenic expression of the anti-apoptotic protein Bcl-2 in p85{alpha}-deficient mice restores the transitional B cell subsets but not the marginal zone subset, and produces a follicular population with an aberrant phenotype. These findings establish a role for PI3K-p85{alpha} in differentiation of both follicular and marginal zone B cells, and suggest that these functions are required not solely for the propagation of anti-apoptotic signals.

Keywords: B lymphocytes; cellular differentiation; signal transduction; spleen; transgenic/knockout.
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