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Science 15 January 1999:
Vol. 283. no. 5400, pp. 390 - 392
DOI: 10.1126/science.283.5400.390
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Reports

Xid-Like Immunodeficiency in Mice with Disruption of the p85alpha Subunit of Phosphoinositide 3-Kinase

Harumi Suzuki, * Yasuo Terauchi, * Mari Fujiwara, Shinichi Aizawa, Yoshio Yazaki, Takashi Kadowaki, Shigeo Koyasu dagger

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.

H. Suzuki, M. Fujiwara, S. Koyasu, Department of Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Y. Terauchi, Y. Yazaki, T. Kadowaki, Department of Internal Medicine, University of Tokyo, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. S. Aizawa, Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 860, Japan.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: koyasu{at}sun.microb.med.keio.ac.jp

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BCR Engagement Induces Fas Resistance in Primary B Cells in the Absence of Functional Bruton's Tyrosine Kinase.
J. R. Tumang, R. S. Negm, L. A. Solt, T. J. Schneider, T. P. Colarusso, W. D. Hastings, R. T. Woodland, and T. L. Rothstein (2002)
J. Immunol. 168, 2712-2719
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Essential Immunoregulatory Role for BCAP in B Cell Development and Function.
T. Yamazaki, K. Takeda, K. Gotoh, H. Takeshima, S. Akira, and T. Kurosaki (2002)
J. Exp. Med. 195, 535-545
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Cooperation of multiple signaling pathways in CD40-regulated gene expression in B lymphocytes.
H. Dadgostar, B. Zarnegar, A. Hoffmann, X.-F. Qin, U. Truong, G. Rao, D. Baltimore, and G. Cheng (2002)
PNAS 99, 1497-1502
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Molecular Balance between the Regulatory and Catalytic Subunits of Phosphoinositide 3-Kinase Regulates Cell Signaling and Survival.
K. Ueki, D. A. Fruman, S. M. Brachmann, Y.-H. Tseng, L. C. Cantley, and C. R. Kahn (2002)
Mol. Cell. Biol. 22, 965-977
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BCR signal through {alpha}4 is involved in S6 kinase activation and required for B cell maturation including isotype switching and V region somatic hypermutation.
S. Inui, K. Maeda, D. R. Hua, T. Yamashita, H. Yamamoto, E. Miyamoto, S. Aizawa, and N. Sakaguchi (2002)
Int. Immunol. 14, 177-187
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Phosphatidylinositol 3-Kinase and NF-kappa B Regulate Motility of Invasive MDA-MB-231 Human Breast Cancer Cells by the Secretion of Urokinase-type Plasminogen Activator.
D. Sliva, M. T. Rizzo, and D. English (2002)
J. Biol. Chem. 277, 3150-3157
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Beyond calcium: new signaling pathways for Tec family kinases.
A. Takesono, L. D. Finkelstein, and P. L. Schwartzberg (2002)
J. Cell Sci. 115, 3039-3048
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Phosphatidylinositol 3-Kinase Suppresses Glucose-Stimulated Insulin Secretion by Affecting Post-Cytosolic [Ca2+] Elevation Signals.
K. Eto, T. Yamashita, Y. Tsubamoto, Y. Terauchi, K. Hirose, N. Kubota, S. Yamashita, J. Taka, S. Satoh, H. Sekihara, et al. (2002)
Diabetes 51, 87-97
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xid mice reveal the interplay of homeostasis and Bruton's tyrosine kinase-mediated selection at multiple stages of B cell development.
M. P. Cancro, A. P. Sah, S. L. Levy, D. M. Allman, M. R. Schmidt, and R. T. Woodland (2001)
Int. Immunol. 13, 1501-1514
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Antigen-receptor cross-linking and lipopolysaccharide trigger distinct phosphoinositide 3-kinase-dependent pathways to NF-{{kappa}}B activation in primary B cells.
H. Bone and N. A. Williams (2001)
Int. Immunol. 13, 807-816
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Inhibition of the MEK/ERK Signaling Pathway Blocks a Subset of B Cell Responses to Antigen.
J. D. Richards, S. H. Dave, C.-H. G. Chou, A. A. Mamchak, and A. L. DeFranco (2001)
J. Immunol. 166, 3855-3864
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The B Lymphocyte-Specific Coactivator BOB.1/OBF.1 Is Required at Multiple Stages of B-Cell Development.
J. Hess, P. J. Nielsen, K.-D. Fischer, H. Bujard, and T. Wirth (2001)
Mol. Cell. Biol. 21, 1531-1539
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I{kappa}b Kinase {alpha} Is Essential for Mature B Cell Development and Function.
T. Kaisho, K. Takeda, T. Tsujimura, T. Kawai, F. Nomura, N. Terada, and S. Akira (2001)
J. Exp. Med. 193, 417-426
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Cutting Edge Commentary: Origins of B-1 Cells.
H. H. Wortis and R. Berland (2001)
J. Immunol. 166, 2163-2166
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Phosphoinositide 3-kinase signalling pathways.
D. Cantrell (2001)
J. Cell Sci. 114, 1439-1445
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B Cell Development Is Arrested at the Immature B Cell Stage in Mice Carrying a Mutation in the Cytoplasmic Domain of Immunoglobulin {beta}.
A. Reichlin, Y. Hu, E. Meffre, H. Nagaoka, S. Gong, M. Kraus, K. Rajewsky, and M. C. Nussenzweig (2001)
J. Exp. Med. 193, 13-24
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Loss of PTEN expression leading to high Akt activation in human multiple myelomas.
T. Hyun, A. Yam, S. Pece, X. Xie, J. Zhang, T. Miki, J. S. Gutkind, and W. Li (2000)
Blood 96, 3560-3568
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