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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{delta} in Signaling by the B-Cell Receptor Complex

Shiann-Tarng Jou,1,{dagger} Nick Carpino,1 Yutaka Takahashi,1 Roland Piekorz,1,2 Jyh-Rong Chao,1 Neena Carpino,1 Demin Wang,1,{ddagger} and James N. Ihle1,2,3*

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 {delta} 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 {delta} isoform of p110 PI3K for the development and function of B cells.

* Corresponding author. Mailing address: Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105. Phone: (901) 495-3422. Fax: (901) 525-8025. E-mail: james.ihle{at}stjude.org.

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

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

Molecular and Cellular Biology, December 2002, p. 8580-8591, Vol. 22, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.24.8580-8591.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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