A crucial role for the p110δ subunit of phosphatidylinositol 3-kinase in B cell development and activation

被引:371
作者
Clayton, E
Bardi, G
Bell, SE
Chantry, D
Downes, CP
Gray, A
Humphries, LA
Rawlings, D
Reynolds, H
Vigorito, E
Turner, M [1 ]
机构
[1] Babraham Inst, Mol Immunol Programme, Lab Lymphocyte Signaling & Dev, Cambridge CB2 4AT, England
[2] COS Corp, Bothell, WA 98021 USA
[3] Univ Dundee, Dept Biochem, Dundee DD1 5EH, Scotland
[4] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[5] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA
[6] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA
关键词
Akt; Btk; calcium; gone targeting; p110; delta;
D O I
10.1084/jem.20020805
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mice lacking the p 1108 catalytic subunit of phosphatidylinositol 3-kinase have reduced numbers of B1 and marginal zone B cells, reduced levels of serum immunoglobulins, respond poorly to immunization with type II thymus-independent antigen, and are defective in their primary and secondary responses to thymus-dependent antigen. p110delta(-/-) B cells proliferate poorly in response to B cell receptor (BCR) or CD40 signals in vitro, fail to activate protein kinase B, and are prone to apoptosis. p110delta function is required for BCR-mediated calcium flux, activation of phosphipaseCgamma2, and Bruton's tyrosine kinase. Thus, p110delta plays a critical role in B cell homeostasis and function.
引用
收藏
页码:753 / 763
页数:11
相关论文
共 63 条
[1]   BLNK mediates Syk-dependent Btk activation [J].
Baba, Y ;
Hashimoto, S ;
Matsushita, M ;
Watanabe, D ;
Kishimoto, T ;
Kurosaki, T ;
Tsukada, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2582-2586
[2]   Activation of phospholipase C-γ by phosphatidylinositol 3,4,5-trisphosphate [J].
Bae, YS ;
Cantley, LG ;
Chen, CS ;
Kim, SR ;
Kwon, KS ;
Rhee, SG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (08) :4465-4469
[3]   Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110α subunit of phosphoinositide 3-kinase [J].
Bi, L ;
Okabe, I ;
Bernard, DJ ;
Wynshaw-Boris, A ;
Nussbaum, RL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (16) :10963-10968
[4]   Early embryonic lethality in mice deficient in the p110β catalytic subunit of PI 3-kinase [J].
Bi, L ;
Okabe, I ;
Bernard, DJ ;
Nussbaum, RL .
MAMMALIAN GENOME, 2002, 13 (03) :169-172
[5]   SHIP modulates immune receptor responses by regulating membrane association of Btk [J].
Bolland, S ;
Pearse, RN ;
Kurosaki, T ;
Ravetch, JV .
IMMUNITY, 1998, 8 (04) :509-516
[6]   Antigen-receptor cross-linking and lipopolysaccharide trigger distinct phosphoinositide 3-kinase-dependent pathways to NF-κB activation in primary B cells [J].
Bone, H ;
Williams, NA .
INTERNATIONAL IMMUNOLOGY, 2001, 13 (06) :807-816
[7]   Differential regulation of B cell development, activation, and death by the Src homology 2 domain-containing 5′ inositol phosphatase (SHIP) [J].
Brauweiler, A ;
Tamir, I ;
Dal Porto, J ;
Benschop, RJ ;
Helgason, CD ;
Humphries, RK ;
Freed, JH ;
Cambier, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (09) :1545-1554
[8]  
Buhl AM, 1999, J IMMUNOL, V162, P4438
[9]   Qualitative regulation of B cell antigen receptor signaling by CD19: Selective requirement for PI3-kinase activation, inositol-1,4,5-trisphosphate production and Ca2+ mobilization [J].
Buhl, AM ;
Pleiman, CM ;
Rickert, RC ;
Cambier, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (11) :1897-1910
[10]   p110 delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes [J].
Chantry, D ;
Vojtek, A ;
Kashishian, A ;
Holtzman, DA ;
Wood, C ;
Gray, PW ;
Cooper, JA ;
Hoekstra, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (31) :19236-19241