Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85 alpha

Phosphoinositide 3-kinase (PI3K) activation has been implicated in many cel lular responses, including fibroblast growth, transformation, survival, and chemotaxis, Although PI3K is activated by several agents that stimulate T and B cells, the role of PI3K in Lymphocyte function is not clear. The mous e gene encoding the PI3K adapter subunit p85 alpha and its splice variants p55 alpha and p50 alpha was disrupted. Most p85 alpha-p55 alpha-p50 alpha(- /-) mice die within days after birth. Lymphocyte development and function w as studied with the use of the RAG2-deficient blastocyst complementation sy stem. Chimeric mice had reduced numbers of peripheral mature B cells and de creased serum immunoglobulin. The B cells that developed had diminished pro liferative responses to antibody to immunoglobulin M, antibody to CD40, and Lipopolysaccharide stimulation and decreased survival after incubation wit h interleukin-A In contrast, T cell development and proliferation was norma l. This phenotype is similar to defects observed in mice lacking the tyrosi ne kinase Btk.