Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha
| Autor: | Frederick W. Alt, Scott B. Snapper, Jonathan Y. Yu, Lewis C. Cantley, David A. Fruman, Laurie Davidson, Claudine M. Yballe |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Lymphocyte T cell Cellular differentiation Morpholines T-Lymphocytes Immunoglobulins Apoptosis Lymphocyte Activation Mice Phosphatidylinositol 3-Kinases Catalytic Domain medicine Agammaglobulinaemia Tyrosine Kinase Bruton's tyrosine kinase Animals Lymphocyte Count Enzyme Inhibitors B cell Phosphoinositide-3 Kinase Inhibitors B-Lymphocytes Multidisciplinary CD40 Phosphoinositide 3-kinase biology Chimera Cell Cycle Protein-Tyrosine Kinases Molecular biology Mice Inbred C57BL medicine.anatomical_structure Immunoglobulin M Chromones Immunology Gene Targeting biology.protein Leukocyte Common Antigens Female Spleen |
| Zdroj: | Science (New York, N.Y.). 283(5400) |
| ISSN: | 0036-8075 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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