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Molecular and Cellular Biology, December 2002, p. 8580-8591, Vol. 22, No. 24
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.24.8580-8591.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Essential, Nonredundant Role for the Phosphoinositide 3-Kinase p110 in Signaling by the B-Cell Receptor Complex

Shiann-Tarng Jou,^1, Nick Carpino,¹ Yutaka Takahashi,¹ Roland Piekorz,^1,2 Jyh-Rong Chao,¹ Neena Carpino,¹ Demin Wang,^1, and James N. Ihle^1,2,3*

Howard Hughes Medical Institute,² Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,¹ Department of Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee 38063³

Received 19 July 2002/ Returned for modification 23 August 2002/ Accepted 12 September 2002

Many receptor and nonreceptor tyrosine kinases activate phosphoinositide 3-kinases (PI3Ks). To assess the role of the isoform of the p110 catalytic subunit of PI3Ks, we derived enzyme-deficient mice. The mice are viable but have decreased numbers of mature B cells, a block in pro-B-cell differentiation, and a B1 B-cell deficiency. Both immunoglobulin M receptor-induced Ca²⁺ flux and proliferation in response to B-cell mitogens are attenuated. Immunoglobulin levels are decreased substantially. The ability to respond to T-cell-independent antigens is markedly reduced, and the ability to respond to T-cell-dependent antigens is completely eliminated. Germinal center formation in the spleen in response to antigen stimulation is disrupted. These results define a nonredundant signaling pathway(s) utilizing the isoform of p110 PI3K for the development and function of B cells.

Present address: Department of Pediatrics, National Taiwan University Hospital, Taipei 100, Taiwan.

Present address: Blood Research Institute and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226.

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