Impaired B Cell Development and Proliferation in Absence of Phosphoinositide 3-Kinase p85α

• Published in: Science (American Association for the Advancement of Science) Vol. 283; no. 5400; pp. 393 - 397
• Main Authors: Fruman, David A., Snapper, Scott B., Yballe, Claudine M., Davidson, Laurie, Yu, Jonathan Y., Alt, Frederick W., Cantley, Lewis C.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 15.01.1999; American Association for the Advancement of Science
• Subjects: Animals; Antibodies; Apoptosis; B lymphocytes; Biological and medical sciences; Cell cycle; Cell lines; Chimeras; Classical genetics, quantitative genetics, hybrids; Developmental biology; DNA probes; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetics of eukaryotes. Biological and molecular evolution; Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; T lymphocytes; Thymocytes; Vertebrata; Immunopathology; Immune response; Targeting; Enzyme; Transferases; Rodentia; Cellular immunity; B-Lymphocyte; Cell differentiation; Immune deficiency; 1-Phosphatidylinositol 3-kinase; Signal transduction; Vertebrata; Mammalia; Gene; Mouse; Alpha-Peptide chain; Mutation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.283.5400.393

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-p50$\alpha^{-/-}$ 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.