Xid-like immunodeficiency in mice with disruption of the p85alpha subunit of phosphoinositide 3-kinase.
Mice with a targeted gene disruption of p85alpha, a regulatory subunit of phosphoinositide 3-kinase, had impaired B cell development at the pro-B cell stage, reduced numbers of mature B cells and peritoneal CD5+ Ly-1 B cells, reduced B cell proliferative responses, and no T cell-independent antibody production. These phenotypes are nearly identical to those of Btk-/- or xid (X-linked immunodeficiency) mice. These results provide evidence that p85alpha is functionally linked to the Btk pathway in antigen receptor-mediated signal transduction and is pivotal in B cell development and functions.
Suzuki
H
H
Department of Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Terauchi
Y
Y
Fujiwara
M
M
Aizawa
S
S
Yazaki
Y
Y
Kadowaki
T
T
Koyasu
S
S
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000917:Antibody Formation; D000950:Antigens, Ly / Q000032:analysis; D000955:Antigens, T-Independent / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D018956:CD5 Antigens / Q000032:analysis; D002470:Cell Survival; D018390:Gene Targeting; D008040:Genetic Linkage; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D009154:Mutation; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D014960:X Chromosome
D000950:Antigens, Ly; D000955:Antigens, T-Independent; D018956:CD5 Antigens; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse