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Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex. Mol Cell Biol 2002 Dec;22(24):8580-91

Date

11/26/2002

Pubmed ID

12446777

Pubmed Central ID

PMC139888

DOI

10.1128/mcb.22.24.8580-8591.2002

Scopus ID

2-s2.0-0037695593   292 Citations

Abstract

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 Ca(2+) 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.

Author List

Jou ST, Carpino N, Takahashi Y, Piekorz R, Chao JR, Carpino N, Wang D, Ihle JN

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antigens, T-Independent
B-Lymphocytes
Calcium
Cells, Cultured
Class I Phosphatidylinositol 3-Kinases
Flow Cytometry
Gene Targeting
Germinal Center
Hematopoietic Stem Cells
Humans
Immunoglobulins
Macromolecular Substances
Mice
Mice, Knockout
Phosphatidylinositol 3-Kinases
Receptors, Antigen, B-Cell
Signal Transduction
Stem Cells
T-Lymphocytes
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5