Essential, nonredundant role for the phosphoinositide 3-kinase p110δ in signaling by the B-cell receptor complex

ST Jou, N Carpino, Y Takahashi… - … and cellular biology, 2002 - Am Soc Microbiol
ST Jou, N Carpino, Y Takahashi, R Piekorz, JR Chao, N Carpino, D Wang, JN Ihle
Molecular and cellular biology, 2002Am Soc Microbiol
Many receptor and nonreceptor tyrosine kinases activate phosphoinositide 3-kinases
(PI3Ks). To assess the role of the δ 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 …
Abstract
Many receptor and nonreceptor tyrosine kinases activate phosphoinositide 3-kinases (PI3Ks). To assess the role of the δ 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 δ isoform of p110 PI3K for the development and function of B cells.
American Society for Microbiology