Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85α

DA Fruman, SB Snapper, CM Yballe, L Davidson… - Science, 1999 - science.org
DA Fruman, SB Snapper, CM Yballe, L Davidson, JY Yu, FW Alt, LC Cantley
Science, 1999science.org
Phosphoinositide 3-kinase (PI3K) activation has been implicated in many cellular
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 mouse gene encoding the PI3K adapter subunit p85α
and its splice variants p55α and p50α was disrupted. Most p85α-p55α-p50α−/− mice die
within days after birth. Lymphocyte development and function was studied with the use of the …
Phosphoinositide 3-kinase (PI3K) activation has been implicated in many cellular 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 mouse gene encoding the PI3K adapter subunit p85α and its splice variants p55α and p50α was disrupted. Most p85α-p55α-p50α−/− mice die within days after birth. Lymphocyte development and function was studied with the use of the RAG2-deficient blastocyst complementation system. Chimeric mice had reduced numbers of peripheral mature B cells and decreased serum immunoglobulin. The B cells that developed had diminished proliferative responses to antibody to immunoglobulin M, antibody to CD40, and lipopolysaccharide stimulation and decreased survival after incubation with interleukin-4. In contrast, T cell development and proliferation was normal. This phenotype is similar to defects observed in mice lacking the tyrosine kinase Btk.
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