研究業績(原著論文・新聞記事)

研究業績(原著論文・新聞記事)

新聞記事

  • 日経産業新聞2019.1.21(PDF)
  • 日本経済新聞2016.10.28(PDF/353KB)
  • 2010年8月の日経と読売に、研究成果が掲載されました。

    日経新聞記事2010.8

    読売新聞記事2010.8

    1.  
    2. Tsubata, T. (2023): The ligand interactions of B cell Siglecs are involved in the prevention of autoimmunity to sialylated self-antigens and in the quality control of signaling-competent B cells. Int. Immunol (in press). doi: 10.1093/intimm/dxad030

      Tsubata, T. (2023): Siglec cis-ligands and their roles in the immune system. Glycobiology  33: 532-544. doi:10.1093/glycob/cwad038

      Wang, Z.-X., Pan, Y.-Q., Li, X., Tsubata, T. and , Xu, R.-H. (2023): Immunotherapy in gastrointestinal cancers: Advances, challenges, and countermeasures. Sci. Bull. 68: 763-766. doi.org/10.1016/j.scib.2023.03.036

      Suganuma, Y., Imamura, A., Ando, H., Kiso, M., Takematsu, H., Tsubata, T. and Ishida, H. (2023): Improved synthesis of CD22-binding sialosides and its application for further development of potent CD22 inhibitors. Glycoconj. J. 40: 225-246. doi.org/10.1007/s10719-023-10098-8

      Tamehiro, K., Kimura, A., Tsubata, T., Takahashi, S. and Suzuki, H. (2022): Anti-oxidative enzyme NAD(P)H quinone oxidoreductase1 (NQO1) controls differentiation of Th17 cells via regulation of intracellular ROS level. PLOS ONE 17 (7): e0272090. doi: 10.1371/journal.pone.0272090

      Wang, Y., Liu, J., Akatsu, C., Zhang, R., Zhang, H., Zhu, H., Liu, K., Zhu, H., Min, Q., Meng, X., Cui, C., Tang, Y., Yu, M., Li, Y., Feng, X., Wei, H., Wen, Z., Ji, S., Weigert, M., Tsubata, T. and Wang, J.-Y. (2022): Lysosomal-associated transmembrane protein 5 mediates immature B cell apoptosis and B-cell tolerance by regulating WWP2-PTEN-AKT pathway. Proc. Natl. Acad. Sci USA. 119 (36): e2205629119. doi: 10.1073/pnas.220562911

      Akatsu, C., Alborzian Deh Sheikh, A., Matsubara, N., Takematsu, H., Schweizer, A., Abdu-Allah, H. H. M., Tedder, T. F., Nitschke, L., Ishida, H. and Tsubata, T. (2022): Inhibitory co-receptor CD22 restores B cell signaling by developmentally regulating Cd45-/- immunodeficient B cells. Sci. Signal. 15 (723): eabf 9570. DOI: 10.1126/scisignal.abf9570


      Tsubata, T (2022): Role of inhibitory B cell co-receptors in B cell self-tolerance to non-protein antigens. Immunol. Rev. 307: 53-65. doi:10.1111/imr.13059

      Li, Y., Tang, Y., Liu, J., Meng, X., Wang, Y., Min, Q., Hong, R., Tsubata, T., Hase, K., and Wang, J.-Y. (2022): Glia maturation factor- is involved in S1P-induced marginal zone B cell chemotaxis and optimal T-independent type II antigen-induced IgM production. Int. Immunol. 34: 35-43. doi: 10.1093/intimm/dxab097

      Long, W., Kunitake, S., Sawada, S., Akiyoshi, K. and Tsubata, T. (2021): Protein antigen conjugated with cholesteryl amino-pullulan nanogel shows delayed degradation in dendritic cells and augmented immunogenicity. Vaccine 39: 7526-7530. doi: 10.1016/j.vaccine.2021.11.047

      Alborzian Deh Sheikh, A, Akatsu, C., Abdu-Allah, H. H. M., Suganuma, Y., Imamura, A., Ando, H., Takematsu, H., Ishida, H. and Tsubata, T. (2021): The protein tyrosine phosphatase SHP-1 (PTPN-6) but not CD45 (PTPR-C) is essential for the ligand-mediated regulation of CD22 in BCR-ligated B cells. J. Immunol. 206: 2544-2551.

    3. Akatsu, C., Alborzian Deh Sheikh, A., Matsubara, N., Takematsu, H., Schweizer, A., Abdu-Allah, H. H. M., Tedder, T. F., Nitschke, L., Ishida, H. and Tsubata, T. (2022): Inhibitory co-receptor CD22 restores B cell signaling by developmentally regulating Cd45-/- immunodeficient B cells. Sci. Signal. 15 (723): eabf 9570.
      DOI: 10.1126/scisignal.abf9570

    Ballet, R., Brennan, M., Brandl, C., Feng, N., Berri, J., Cheng, J., Ocón, B., Alborzian Deh Sheikh, A., Marki, A., Bi,Y., Abram, C. L., Lowell, C. A., Tsubata, T., Greenberg, H. B., Macauley, M. S., Ley, K., Nitschke, L., Butcher. E. C. (2021) CD22-Shp1 phosphatase axis controls integrin β7 display and B cell function in mucosal immunity. Nat. Immunol:22:381-390 

    Tsugawa, N., Yamada, D., Watabe, T., Onizawa, M, Wang, S., Nemoto, Y., Oshima, S., Tsubata, T., Adachi, T., Karasuyama, H., Watanabe, M., Blumberg, R., Okamoto, R., and Nagaishi, T. (2021) CEACAM1 specifically suppresses B cell receptor signaling-mediated activation. Biochem. Biophys. Res. Commun. 535: 99-105.

    Alborzian Deh Sheikh, A., Gomaa, S., Li, X., Routledge, M., Saigo, K., Numoto, N., Angata, T., Hitomi, Y., Takematsu, H., Tsuiji, M., Ito, N., Kusunoki, S. and Tsubata, T. (2021): A Guillain-Barré syndrome-associated SIGLEC10 rare variant impairs its recognition of gangliosides. J. Autoimmun. 116: 102571.

    Tsubata, T. (2020): Involvement of reactive oxygen species (ROS) in BCR signaling as a second messenger. In “B Cells in Immunity and Tolerance” ed. by Ji-Yang Wang, Springer pp. 37-46.

    Alborzian Deh Sheikh, A., Akatsu, C. and Tsubata, T. (2020): Identification of Siglec Cis-ligands by Proximity Labeling. In “Lectin Purification and Analysis: Methods and Protocols” ed. by Jun Hirabayashi, Springer pp. 75-83.

    Hong, R., Lai, N., Xiong, E., Ouchida, R., Sun, J., Zhou, Y., Tang, Y., Hikida, M., Tsubata, T., Tagawa, M., Wang, Y. and J.-y. Wang (2020): Distinct roles of BCNP1 in B cell development and activation. Int. Immunol. 32: 17-26.

    Xiong, E., Li, Y., Min, Q., Cui, C., Hong, R., Lai, N., Wang, Y., Sun, J., Matsumoto, R., Takahashi, D., Hase, K., Shinkura, R., Tsubata, T., Wang, J.-Y. (2019): MZB1 promotes the secretion of J chain-containing dimeric IgA and is critical for the suppression of gut inflammation. Proc. Natl. Acad. Sci. USA. 116: 13480-13489.

    Hong, R., Lai, N., Ouchida, R., Xiong, E., Zhou, Y., Hikida, M., Tsubata, T., Wang, Y. and Wang, J.-y. (2019): The B cell novel protein 1 regulates BCR signaling and B cell apoptosis. Eur. J. Immunol.49: 911-917.

    Feng, Y.-y., Tang, M., Suzuki, M., Gunasekara, C., Anbe, Y., Hiraoka, Y., Liu. J., Grasberger, H., Ohkita, M., Matsumura, Y., Wang, J.-y. and Tsubata, T. (2019): Essential role of NADPH oxidase-dependent production of reactive oxygen species in maintenance of sustained B cell receptor signaling and B cell proliferation. J. Immunol. 202: 2546-2557.

    Tsubata, T (2019): Development of Siglec Regulators. In “Glycoscience: Basic Science to Application” ed. by Naoyuki Taniguchi , Tamao Endo, Jun Hirabayashi and Shoko Nishihara, Springer (in press).

    Tsubata, T. (2019): CD72 is a negative regulator of B cell responses to nuclear lupus self-antigens and development of SLE. Immune Netw. 19:e1.

    Tsubata, T. (2018): Ligand recognition determines the role of inhibitory B cell co-receptors in the regulation of B cell homeostasis and autoimmunity. Front Immunol. 9: 2276.

    Lino, A. C., Dang, V. D., Lampropoulou, V., Welle, A., Joedicke, J., Pohar, J., Simon, Q., Thalmensi, J., Baures, A., Fluehler, V., Sakwa, I., Stervbo, U., Ries, S., Jouneau, L., Boudinot., P., Tsubata, T. Adachi, T., Hutloff, A., Doener, T., Zimber-Strobl, U., de Vos, A. F., Dahlke, K., Loh, G., Komiotis, S., Goosmann, C., Weill, J.-C., Raynaud, C.-A., Kaufmann, S. H. E., Walter, J. and Fillatreau, S. (2018) : LAG-3 expression identifies immunosuppressive natural regulatory plasma cells. Immunity. 49: 120-133.

    Li, S., Liu, J., Min, Q., Ikawa, T., Yasuda, S., Yang, Y., Wang, Y.-Q., Tsubata, T., Zhao, Y. and Wang, J.-Y. (2018): Kelch-like protein 14 promotes B-1a but suppresses B-1b cell development. Int. Immunol. 30: 311-318.

    Matsubara, N., Imamura, A., Yonemizu, T., Akatsu, C., Yang, H., Ueki, A., Watanabe, N., Abdu-Allah, H., Numoto, N., Takematsu, H., Kitazume, S., Tedder, T. F., Marth, J. D., Ito, N., Ando, H., Ishida, H., Kiso, M. and Tsubata, T. (2018): CD22-binding synthetic sialosides regulate B lymphocyte proliferation through CD22 ligand-dependent and independent pathways, and enhance antibody production in mice. Front. Immunol. 9: 820.

    Liu, J., Zhu, H., Qian, J., Xiong, E., Zhang, L., Chu, Y., Kubagawa, H., Tsubata, T. and Wang, J.-Y. (2018): FcµR promotes the survival and activation of marginal zone B cells and protects mice against bacterial sepsis. Front. Immunol. 9: 160.

    Alborzian Deh Sheikh, A., Akatsu, C., Imamura, A., Abdu-Allah, H. H. M., Takematsu, H., Ando, H., Ishida, H. and Tsubata, T. (2018): Proximity labeling of cis-ligands of CD22/Siglec-2 reveals stepwise α2,6 sialic acid-dependent and -independent interactions. Biochem. Biophys. Res. Comm. 495: 854-859.

    Tsubata, T. (2018): Negative regulation of B cell responses and self-tolerance to RNA-related lupus self-antigen. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 94 (1) :35-44 .

    Liu, J., Xiong, E., Zhu, H., Mori, H., Yasuda, S., Kinoshita, K., Tsubata, T. and Wang, J.-Y. (2017): Efficient induction of Ig gene hypermutation in ex vivo-activated primary B cells. J. Immunol. 199(9):3023-3030.

    Tsubata, T (2017): B cell tolerance and autoimmunity. F1000Research 6 (F1000 Faculty Rev.): 391.

    Akatsu, C., Shinagawa, K., Numoto, N., Liu, Z., Konuscan, A.U., Aslam, M., Phoon, S., Adachi, T., Furukawa, K., Ito, N. and Tsubata. T. (2016): CD72 negatively regulates B lymphocyte responses to the lupus-related endogenous Toll-like receptor 7 ligand Sm/RNP. J. Exp. Med. 213: 2691-2706.

    Li, Y., Takahashi, Y., Fujii, S., Suzuki, A., Tsubata, T., Hase, K. and Wang, J.-Y.(2016): EAF2 mediates germinal center B cell apoptosis to suppress excessive immune responses and prevent autoimmunity. Nature Communications. 3;7:10836.

    Tsubata, T. (2016): CD22 and CD72 are inhibitory receptors dominantly expressed in B lymphocytes and regulate systemic autoimmune diseases. Z. Rheumatol. 75: 86-89.

    Muro. R., Nitta. T., Okada. T., Ideta. H., Tsubata. T. and Suzuki. H. (2015): The Ras GTPase-activating protein Rasal3 supports survival of naive T cells. PLoS ONE.10: e0119898.

    Ouchida. R., Lu. Q., Liu. J., Li. Y., Chu. Y., Tsubata. T. and Wang, J.-Y. (2015): FcμR interacts and cooperates with the B cell receptor to promote B cell survival. J. Immunol. 194: 3096-3101

    Tsubata, T. (2014): Siglecs and B cell regulation. In: Taniguchi N., Endo T., Hart G., Seeberger P., Wong C. (Ed.) Glycoscience: Biology and Medicine: SpringerReference (www.springerreference.com). Springer-Verlag Berlin Heidelberg. 2014-04-01 06:48:34 UTC

    Kawai, Y., Ouchida, R., Yamasaki, S., Dragone, L., Tsubata, T. and Wang, J.-Y. (2014): LAPTM5 promotes lysosomal degradation of intracellular but not the cell surface CD3ζ. Immunol. Cell Biol. 92:527-534.

    Naito-Matsui, Y., Takada, S., Kano, Y., Iyoda, T., Sugai, M, Shimizu, A., Inaba, K., Nitschke, L., Tsubata, T., Oka, S., Kozutsumi, Y. and Takematsu, H. (2014): Functional evaluation of activation-dependent alterations in the sialogylcan composition of T cells. J. Biol. Chem. 289: 1564-1579.

    Aslam, M., Kishi, Y. and Tsubata, T. (2013): Excess CD40L does not rescue anti-DNA B cells from clonal anergy. F1000 Research 2:218.

    Xu, M., Hou, R., Sato-Hayashizaki, A., Man, R., Zhu, C., Wakabayashi, C, Hirose, S., Adachi, T. and Tsubata, T. (2013): CD72c is a modifier gene that regulates Faslpr-induced autoimmune disease. J. Immunol. 190:5436-45.

    Koni, P., Bolduc, A., Takezaki, M., Amtani, Y., Huang, L., Nutt S. L., Kamanaka, M., Flavell, R. A., Mellor A. L, Tsubata, T., Shimoda, M. (2013): Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction. J. Immunol. 190: 3189-3196.

    Maeno, E., Tsubata, T. and Okada, Y (2012): Apoptotic volume decrease (AVD) is independent of mitochondrial dysfunction and initiator caspase activation. Cells 1: 1156-1167.

    Hitomi, Y., Adachi, T., Tsuchiya, N., Honda, Z.-I., Tokunaga, K and Tsubata, T. (2012): Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic resticulum. BMC Immunol. 13: 72.

    Klionsky, D.J., Abdalla, F. C. Tsubata, T. et al. (2012): Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8: 1-100.

    Kishi, Y., Higuchi, T., Phoon, S., Kamiya, K., Riemekasten, G., Akiyoshi, K., Weigert, M. and Tsubata, T. (2012): Apoptotic marginal zone deletion of anti-Sm/ribonucleoprotein B cells. Proc. Natl. Acad. Sci. USA. 109(20) : 7811-6

    Tsubata T.(2012): Role Of Inhibitory Bcr Co-Receptors In Immunity. Infect Disord Drug Targets. Mar 6.

    Tsubata, T. (2011): ЯПОНИЯ ПОСЛЕ ЗЕМЛЕТРЯСЕНИЯ, ЦУНАМИ И КАТАСТРОФЫ В ФУКУСИМЕ. РОССИЯ И ГЕРМАНИЯ 2:30-31.

    Magesh, S., Ando, H., Tsubata, T., Ishida, H. and Kiso, M. (2011): High-affinity ligands of Siglec receptors and their therapeutic potentials. Current Medicinal Chemistry 18: 3537-3550.

    Abdu-Allah, H. H. M, Watanabe, K., Kanie, O., Tsubata, T. Ishida, H. and Kiso, M. (2011). Design and synthesis of multivalent heterobifunctional CD22-ligand as a potential immunomodulator. Synthesis 18: 2968-2974.

    Poe, J. C., Smith , S. H., Haas, K. M., Yanabe, K., Tsubata, T., Matsushita, T. and Tedder, T. F. (2011) Amplified B lymphocyte CD40 signaling drives regulatory B10 cell expansion in mice. PLoS ONE 6: e22464.

    Abdu-Allah, H. H. M., Watanabe, K., Completo, G. C., Sadagopan, M., Hayashizaki, K., Takaku, C., Tamanaka, T., Takematsu, H., Kozutsumi, Y., Paulson, J.C., Tsubata, T., Ando, H., Ishida, H. and Kiso, M. (2011): CD22-antagonists with nanomolar potency: The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold. Bioorg. Med. Chem. 19: 1966-1971.

    Watanabe, K., Tsuchiya, Y., Kawaguchi, Y., Sawada, S.-i., Ayame, H., Akiyoshi, K. and Tsubata, T. (2011): The use of cationic nanogels to deliver proteins to myeloma cells and primary T lymphocytes that poorly express heparan sulfate. Biomaterials 32: 5900-5905.

    Man, R.-Y., Onodera, T., Komatsu, E. and Tsubata, T. (2010): Augmented B Lymphocyte Response to Antigen in the Absence of Antigen-induced B Lymphocyte Signaling in an IgG-transgenic Mouse Line. PLoS One 5: 8815.

    Ishiura, N., Nakashima, H., Watanabe, R., Kuwano, Y., Adachi, T., Takahashi, Y., Tsubata, T., Okochi, H., Tamaki, K., Tedder, T. F. and Fujimoto M. (2010): Differential phosphorylation of functional tyrosines in CD19 modulates B lymphocyte activation. Eur. J. Immunol. 40: 1192-1204.

    Kishi, Y., Aiba, Y., Higuchi, T., Furukawa, K., Tokuhisa, T., Takemori, T. and Tsubata, T. (2010): Augmented antibody response with premature germinal center regression in CD40L-transgenic mice. J. Immunol. 185: 211-219.

    Bolduc, A., Long, E., Stapler, D., Cascalho, M., Tsubata, T. Koni, P. A. and Shimoda, M. (2010): Constitutive CD40L expression on B cells prematurely terminates germinal center response and leads to augmented plasma cell production in T cell areas. J. Immunol. 185: 220-230.

    Watanabe, K. and Tsubata, T. (2009): Autophagy connects antigen receptor signaling to costimulatory signaling in B lymphocytes. Autophagy.5: 108-110.

    Toda, M., Hisano, R., Yurugi, H., Akita, K., Maruyama, K., Inoue, M., Adachi, T., Tsubata, T. and Nakada, H. (2009): Ligation of tumor-produced mucins to CD22 dramatically impairs splenic marginal zone B cells. Biochem J. 417:673-683.

    Hou, R., Ohtsuji, M., Ohtsuji, N., Zhang, L., Adachi, T., Hirose, S. and Tsubata, T. (2009): The centromeric interval of chromosome 4 derived from C57BL/6 mice accelerates type 1 diabetes in NOD.CD72b congenic mice. Biochem. Biophys. Res. Comm. 380: 193-197.

    Yanaba, K., Bouaziz, J.-D., Matsushita, T., Tsubata, T., and Tedder, T. F. (2009): The development and function of regulatory B cells expressing IL-10 requires antigen receptor diversity and TLR signals. J. Immunol. 182: 7459-7472.

    Abdu-Allah, H. H. M., Watanabe, K., Hayashizaki, K., Iwayama, Y., Takematsu, H., Kozutsumi, Y., Tsubata, T., Ishida, H. and Kiso, M (2009): Synthesis of biotinylated sialoside to probe CD22-ligand interactions. Tetrahedron Lett. 50: 4488-4491.

    Engels, N., König, L. M., Heemann, C., Lutz, J., Tsubata, T., Griep, S., Scharader, V. and Wienands, J. (2009): Recruitment of the cytoplasmic adaptor Grb2 to surface IgG and IgE provides antigen receptor-intrinsic costimulation to class-switched B cells. Nature Immunol. 10: 1018-1025.

    Abdu-Allah, H. H. M., Watanabe, K., Hayashizaki, K., Takaku, C., Tamanaka, T., Takematsu, H., Kozutsumi, Y., Tsubata, T., Ishida, H. and Kiso, M. (2009): Potent small molecule mouse CD22 inhibitors: exploring the interaction of the residue at C-2 of sialic acid scaffold. Bioorg. Med. Chem. Lett. 19: 5573-5575

    Yan, B.-C., Adachi, T. and Tsubata, T.(2008): ER stress is involved in B cell antigen receptor ligation-induced apoptosis. Biochem. Biophys. Res. Comm. 365:143-148.

    Onodera, T., Poe, J. C., Tedder, T. F. and Tsubata, T. (2008): CD22 regulates time course of both B cell division and antibody response. J. Immunol. 180: 907-913.

    Zhu, C., Fujimoto, M., Sato, M., Yanagisawa, T. and Tsubata, T. (2008): Novel binding site for SH2-containing protein tyrosine phosphatase-1 in CD22 activated by B Lymphocyte stimulation with antigen. J. Biol. Chem. 283: 1653-1659.

    Adachi, T. and Tsubata, T. (2008): FRET-based Ca2+ measurement in B lymphocyte by flow cytometry and confocal microscopy. Biochem. Biophys. Res. Comm. 367: 377-382.

    Watanabe, K., Ichinose, S., Hayashizaki, K. and Tsubata, T. (2008): Induction of autophagy by B cell antigen receptor stimulation and its inhibition by costimulation. Biochem. Biophys. Res. Comm. 374: 274-281

    Tsubata, T. (2008). Siglec-2 is a key molecule for immune response. In “Experimental Glycoscience, Glycobiology” (ed by N. Taniguchi, A. Suzuki, Y. Ito, H. Narimatsu, T. Kawasaki and S. Hase) p. 167-170, Springer.

    Abdu-Allah, H. H. M., Tamanaka, T., Yu, J., Lu, Z., Sadagopan, M., Adachi. T., Tsubata, T., Kelm, S., Ishida, H. and Kiso, M. (2008): Design, synthesis, and structure-activity relationships of novel series of sialosides as CD22-specific inhibitors. J. Med. Chem. 51: 6665-6681.

    Sato, M., Adachi, T. and Tsubata, T. (2007): Augmentation of signaling through BCR containing IgE but not that containing IgA due to lack of CD22-mediated signal regulation. J. Immunol. 178: 2901-2907.

    Yu, J., Sawada, T., Adachi, T., Gao, X., Takematsu, H., Kozutsumi, Y., Ishida, H., Kiso, M. and Tsubata, T. (2007): Synthetic glycan ligand excludes CD22 from antigen receptor-containing lipid rafts. Biochem. Biophys. Res. Comm. 360: 759-764

    Adachi, T., Wienands, J., Tsubata, T. and Kurosaki, T. (2007): Interdomain A is crucial for ITAM-dependent and -independent regulation of Syk. Biochem. Biophys. Res. Comm. 364: 111-7

    Devi, S. S., Hagiyama, H., Adachi, T., Miyasaka, N. and Tsubata, T. (2006): The tumor suppressor p53 is not required for antigen receptor-mediated apoptosis of B lymphocytes. Signal Transduction 6: 54-61.

    Akagawa, M., Ito, S., Toyoda, K., Ishii, Y., Tatsuda, E., Shibata, T., Kawai, Y., Ishino, K., Kishi, Y., Adachi, T., Tsubata, T., Takasaki, Y., Hattori, N., Matsuda, T. and Uchida, K. (2006): Bispecific antibodies against modified protein and DNA with oxidized lipids. Proc. Natl. Acad. Sci. USA. 103: 6160-5.

    Tsubata, T. (2006): B cell abnormality and systemic lupus erythematosus. APLAR J. Rheum. 9: 372-376

    Tsubata, T. (2005): B cell abnormality and autoimmune disorders. Autoimmunity 38: 331-337.

    Hirai, H., Adachi, T., and Tsubata, T. (2004): Involvement of cell cycle progression in survival signaling through CD40 in B lymphocyte line WEHI-231. Cell Death Differ. 11: 261-269.

    Kawamura, T., Kanai, T., Dohi, T., Uraushihara, K., Totsuka, T., Iiyama, R., Taneda, C., Yamazaki, M., Nakamura, T., Higuchi, T., Aiba, Y., Tsubata, T. and Watanabe, M. (2004): Ectopic CD40 ligand expression on B cells trigger intestinal inflammation. J. Immunol. 172: 6388-6397.

    Nitschke, L. and Tsubata, T. (2004): Molecular interactions regulate BCR signal inhibition by CD22 and CD72. Trends Immunol. 25: 543-550.

    Suzuki, A, Kaisho, T., Ohishi, M., Tsukio-Yamaguchi, M., Tsubata, T., Koni, P. A., Sasaki, T., Mak, T. W., and Nakano, T. (2003): Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination. J. Exp. Med. 197: 657-667.

    Hokazono, Y., Adachi, T., Wabl, M., Tada, N., Amagasa, T., and Tsubata, T. (2003): Inhibitory Co-receptors Activated by Antigens but Not by Anti-immunoglobulin Heavy Chain Antibodies Install Requirement of Co-stimulation through CD40 for Survival and Proliferation of B cells. J. Immunol. 171: 1835-1843.

    Higuchi, T., Aiba, Y., Nomura, T., Matsuda, J., Mochida, K., Suzuki, M., Kikutani, H., Honjo, T., Nishioka, K. and Tsubata T. (2002): Cutting Edge: Ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease. J. Immunol. 168: 9-12.

    Wakabayashi, C., Adachi, T., Wienands, J. and Tsubata, T. (2002): A distinct signaling pathway used by the IgG-containing B cell antigen receptor. Science. 298: 2392-2395.

    抗体には、免疫応答の初期に産生されるIgM型(クラス)抗体、感染防御能の高いIgGクラスの抗体、消化管免疫に関係するIgAクラス,寄生虫感染やアレルギーに関係するIgEクラスがあります。今回の論文では、抗体産生細胞の活性化制御機構が抗体のクラスによって異なることを世界に先駆けて明らかにしました。この機構には膜型レクチン分子CD22/Siglec2が関与します。この機構を人為的に制御することができるようになれば、どのようなクラスの抗体が産生されるかを制御することが可能になります。

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    2001年以前の業績

    Tsubata, T., Wakabayashi, C. and Adachi, T. (2001): Regulation of B cell antigen receptor signaling by CD72. In “Activating and Inhibitory Immunoglobulin-like Receptors” (ed. by Max D. Cooper, Toshiyuki Takai, and Jeffrey V. Ravetch) p. 123-128, Sprnger-Verlag Tokyo.

    Suzuki, A., Tsukio-Yamaguchi, M., Ohteki, T., Sasaki, T., Kaisho, T., Kimura, Y., Yoshida, R., Wakeham, A., Higuchi, T., Fukumoto, M., Tsubata, T., Ohashi, P., Koyasu, S., Penninger, J. M., Nakano, T. and Mak, T. W. (2001): T cell-specific loss of Pten leads to defects in central and peripheral tolerance. Immunity 14: 523-534.

    Adachi, T., Wienands, J., Wakabayashi, C., Yakura, H., Reth, M. and Tsubata, T. (2001): SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates. J. Biol. Chem. 276: 26648-26655.

    Tsubata, T. (2001): Molecular mechanisms for apoptosis induced by signaling through the B cell antigen receptor. Int. Rev. Immunol. 20: 791-803.

    Adachi, T., Wakabayashi, C., Nakayama, T., Yakura, H., and Tsubata T. (2000): CD72 negatively regulates signaling through the antigen receptor of B cells. J. Immunol. 164: 1223-1229.

    Tsubata, T., and Honjo, T. (2000): B cell tolerance and autoimmunity. Rev. Immunogenet.. 2: 18-25.

    Yoshida, T., Higuchi, T., Hagiyama, H., Strasser, A., Nishioka, K., and Tsubata, T. (2000): Rapid B cell apoptosis induced by antigen receptor ligation does not require Fas (CD95/APO-1), the adapter protein FADD/MORT1 or CrmA-sensitive caspases but is defective in both MRL-+/+ and MRL-lpr/lpr mice. Int. Immunol. 12: 517-526.

    Nagaoka, H., Takahashi, Y., Hayashi, R., Nakamura, T., Ishii, K., Matsuda, J.-I., Ogura, A., Shirakata, Y., Karasuyama, H., Sudo, T., Nishikawa, S.-I., Tsubata, T., Mizuochi, T., Asano, T., Sakano, H., and Takemori, T. (2000): Ras mediates effector pathways responsible for pre-B cell survival, which is essential for the developmental progression to the late pre-B cell stage. J. Exp. Med. 192: 171-181.

    Tsubata, T. (1999): Apoptosis of mature B cells. Int. Rev. Immunol. 18: 347-365.

    Hagiyama, H., Adachi, T., Yoshida, T., Nomura, T, Miyasaka, N., Honjo, T., and Tsubata, T. (1999): Signaling through the antigen receptor of B lymphocytes activates a p53-independent pathway of c-Myc-induced apoptosis. Oncogene 18: 4091-4098.

    Tsubata, T. (1999): Co-receptors on B lymphocytes. Curr. Opin. Immunol. 11: 249-255.

    Watanabe N., Nomura, T., Takai, T., Chiba, T., Honjo, T. and Tsubata, T. (1998): Antigen receptor cross-linking by anti-immunoglobulin antibodies coupled to cell surface membrane induces rapid apoptosis of normal spleen B cells. Scand. J. Immunol.. 47: 541-547.

    Adachi, T., Flaswinkel, H., Yakura, H., Reth, M., and Tsubata, T. (1998): The B cell surface protein CD72 recruits the tyrosine phosphatase SHP-1 upon tyrosine phosphorylation. J. Immunol. 160: 4662-4665.

    Adachi, T., Flaswinkel, H., Yakura, H., Reth, M., and Tsubata, T. (1998): The B cell surface protein CD72 recruits the tyrosine phosphatase SHP-1 upon tyrosine phosphorylation. In “Proceedings of 10th International Congress of Immunology “ (ed. by G.P.Talwar, I, Nath, N.K.Ganguly, K.V.S.Rao) p.341-344. Monduzzi Editore S.p.A., Bologna.

    1997年以前の主要論文(鍔田武志)

    Han, H., Nomura, T., Honjo, T., and Tsubata, T. (1997): Involvement of the cyclin-dependent kinase inhibitor p27Kip1 in negative signaling through the antigen-receptor of B lymphocytes. Leukemia 11 (Supp 3): 367-369.

    Tsubata T., Hagiyama, H., Yoshida, T., Han, H., and Honjo, T. (1997): Involvement of p27Kip1 in negative signaling through the antigen-receptor of B lymphocytes reversed by CD40 signaling. In “Kinases and Phosphatases in Lymphocyte and Neuronal Signaling” (ed. by H. Yakura) p. 336-337. Springer-Verlag, Tokyo.

    Agata, Y., Kawasaki, A., Nishimura, H., Ishida, Y., Tsubata, T., Yagita, H., and Honjo, T. (1996): Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int. Immunol. 8: 765-772.

    Nomura, T., Han, H., Howard, M. C., Yagita, H., Yakura, H., Honjo, T., and Tsubata, T. (1996): Antigen receptor-mediated B cell death is blocked by signaling via CD72 or treatment with dextran sulfate and is defective in autoimmunity-prone mice. Int. Immunol. 8: 867-875.

    Shinkura, R., Matsuda, F., Sakiyama, T., Tsubata, T., Hiai, H., Paumen, M., Miyawaki, S., and Honjo, T. (1996): Defects of somatic hypermutation and class switching in alymphoplasia (aly) mutant mice. Int. Immunol. 8: 1067-1075.

    Han, H., Nomura, T., Honjo, T., and Tsubata, T. (1996): Differential modulation of cyclin-dependent kinase inhibitor p27Kip1 by negative signaling via the antigen receptor of B cells and positive signaling via CD40. Eur. J. Immunol. 26: 2425-2432.

    Tsubata, R., Tsubata, T., Hiai, H., Shinkura, R., Matsumura, R., Sumida, T., Miyawaki, S., Ishida, H., Kumagai, S., Nakao, K., and Honjo, T. (1996): Autoimmune Disease of Exocrine Organs in Immunodeficient alymphoplasia mice: a spontaneous model for Sjögren’s syndrome. Eur. J. Immunol. 26: 2742-2748.

    Furukawa, M., Sakamoto, A., Kita, Y., Ohishi, Y., Matsumura, R., Tsubata, R., Tsubata, T. Iwamoto, I., Saitoh, Y., and Sumida, T. (1996): T cell receptor repertoire of infiltrating T cells in lachrymal glands, salivary glands, and kidneys from alymphoplasia (aly) mutant mice: a new model for Sjögren’s syndrome. Br. J. Rheumatol. 35: 1223-1230

    Tsubata, T. (1995): B-1 cells (Ly-1 or CD5+ B cells), apoptosis and autoimmunity. In "Apoptosis and the Immune Response" (ed. by C. Gregory) p.217-256, John Wiley & Sons., New York.

    Li, H., Akamizu, T., Okuda, J., Sugawa, H., Matsuda, F., Tsubata, T., and Mori, T. (1995): Isolation of Epstein-Barr-virus-transformed lymphocytes producing IgG class monoclonal antibodies using a Magnetic Cell Separator (MACS): Preparation of thyroid-stimulating IgG antibodies from patients with Graves' disease. Biochem. Biophys. Res. Commun. 207: 985-993.

    Murakami, M., Yoshioka, H., Shirai, T., Tsubata, T., and Honjo, T. (1995): Prevention of autoimmune symptoms in autoimmune-prone mice by elimination of B-1 cells. Int. Immunol. 7: 877-882.

    Nisitani, S., Tsubata, T., Murakami, M., and Honjo, T. (1995): Administration of interleukins 5 or 10 activates peritoneal B-1 cells and induces autoimmune hemolytic anemia in anti-erythrocyte autoantibody transgenic mice. Eur. J. Immunol. 25: 3047-3052.

    Tsubata, T., Murakami, M., Nisitani, S. and Honjo, T. (1995): Molecular mechanisms for B lymphocyte selection: induction and regulation of antige-receptor-mediated apoptosis of mature B cells in normal mice and their defect in autoimmunity-prone mice. “The Role of Apoptosis in Development, Tissue Homeostasis and Malignancy” (ed. by T. M. Dexter, . C. Raff and A. H. Wyllie) p. 61-66 Chapman & Hall, London.

    Tsubata, T., Murakami, M. and Honjo, T. (1994): Antigen-receptor cross-linking induces peritoneal B-cell apoptosis in normal but not autoimmunity-prone mice. Curr. Biol. 4: 8-17.

    Murakami, M., Tsubata, T. and Honjo, T. (1994): Ly-1 B cells as a component of gut associated lymphoid tissues for mucosal immunity. In "Current Topics in Mucosal Immunology 1993" (ed. by M. Tsuchiya, J. Yodoi, T. Hibi and S. Miura), pp.139-142, Elsevier Science Publishers B. V., Amsterdam.

    Shinkura, R., Tsubata, T., Murakami, M., Miyawaki, S., Usui, T., Yoshioka, H. and Honjo, T. (1994): Involvement of Peyer's patches in the generation of a subset of peritoneal B lymphocytes. In "Current Topics in Mucosal Immunology 1993" (ed. by M. Tsuchiya, J. Yodoi, T. Hibi and S. Miura), pp.271-273, Elsevier Science Publishers B. V., Amsterdam.

    Nisitani, S., Tsubata, T. and Honjo, T. (1994): Lineage marker-negative lymphocyte precursors from embryonic stem cells in vitro differentiate into mature lymphocytes in vivo. Int. Immunol. 6: 909-916.

    Murakami, M., Tsubata, T., Shinkura, R., Nisitani, S., Okamoto, M., Yoshioka, H., Usui, T., Miyawaki, S. and Honjo, T. (1994): Oral administration of lipopolysaccharides activates B-1 cells in the peritoneal cavity and lamina propria of the gut and induces autoimmune symptoms in an autoantibody transgenic mouse. J. Exp. Med. 180: 111-121.

    Tsubata, T., Murakami, M., Nisitani, S. and Honjo, T. (1994): Molecular mechanisms for B lymphocyte selection: induction and regulation of antige-receptor-mediated apoptosis of mature B cells in normal mice and their defect in autoimmunity-prone mice. Proc. R. Soc. Lond. B. 345: 297-301.

    Murakami, M., Tsubata, T., Shinkura, R., Usui, T., Yoshioka, H., Miyawaki, S. and Honjo, T. (1994): B-1 cells as a component of gut associated lymphoid tissues for mucosal immunity. In "Current Advances in Digestive Disease" (ed. by Y. Yoshida, Y. Murata) p. 75-86, Churchill Livingstone, Tokyo,.

    Tsubata, T., Wu, J. and Honjo, T. (1993): B-cell apoptosis induced by antigen receptor crosslinking is blocked by T-cell signal through CD40. Nature 364: 645-648.

    Nisitani, S., Tsubata, T., Murakami, M., Okamoto, M. and Honjo, T. (1993): The bcl-2 gene product inhibits clonal deletion of self-reactive B lymphocytes in the periphery but not in the bone marrow. J. Exp. Med. 178: 1247-1254.

    Okamoto, M., Murakami, M., Shimizu, A., Ozaki, S., Tsubata, T., Kumagai, S. and Honjo, T. (1992): A transgenic model of autoimmune hemolytic anemia. J. Exp. Med. 175: 71-79.

    Murakami, M., Tsubata, T., Okamoto, M., Shimizu, A., Kumagai, S., Imura, H. and Honjo, T. (1992): Antigen-induced apoptotic death of Ly-1 B cells responsible for autoimmune disease in transgenic mice. Nature 357: 77-80.

    Tsubata, T., Tsubata R. and Reth, M. (1992): Crosslinking of the cell surface immunoglobulin (-surrogate light chains complex) on pre-B cells induces activation of V gene rearrangements at the immunoglobulin  locus. Int. Immunol. 4: 637-641.

    Reth, M., Wienands, J., Tsubata, T. and Hombach J. (1991): Identification of components of the B cell antigen receptor complex. Adv. Exp. Med. Biol. 292: 207-214.

    Tsubata, T. and Nishikawa, S.-I. (1991): Molecular and cellular aspects of early B-cell development. Curr. Opin. Immunol. 3: 186-192.

    Tsubata, T., Tsubata, R. and Reth, M. (1991): Cell surface expression of the short immunoglobulin  chain (D protein) in murine pre-B cells is differently regulated from that of the intact  chain. Eur. J. Immunol. 21: 1351-1355.

    Iwai, K., Tsubata, T., Katsura, Y., Kumagai, S. and Imura, H. (1991): Qualitative difference of anti-DNA antibody-producing cell precursors in the pre-immune B cell repertoire between normal and lupus-prone mice. Clin. Exp. Immunol. 86: 106-111

    Hombach, J., Tsubata, T., Leclercq, L., Stappert, H. and Reth, M. (1990): Molecular components of the B-cell antigen receptor complex of the IgM class. Nature. 343: 760-762.

    Tsubata, T. and Reth, M. (1990): The products of pre-B specific genes (5 and VpreB) and the immunoglobulin  chain form a complex that is transported onto the cell surface. J. Exp. Med. 172: 973-976.

    Kumagai, S., Ishida, H., Iwai, K., Tsubata, T., Umehara, H., Ozaki, S., Suginoshita, T., Araya, S. and Imura, H. (1989): Possible different mechanisms of B cell activation in systemic lupus erythematosus and rheumatoid arthritis: opposite expression of low-affinity receptors for IgE (CD23) on their peripheral B cells. Clin. Exp. Immunol. 78: 348-353.

    Hombach, J., Tsubata, T., Leclercq, L., Stappert, H. and Reth, M. (1989): Molecular components of the IgM antigen receptor complex. In "Progress in Immunology VII" (ed. by F. Melchers et al.) pp.659-662. Springer-Verlag, Berlin.

    Tsubata, T., Nishikawa, S.-I., Katsura, Y., Kumagai, S. and Imura, H. (1988): B cell repertoire for anti-DNA antibody in normal and lupus mice: Differential expression of precursor cells for high and low affinity anti-DNA antibodies. Clin. Exp. Immunol. 71: 50-55.

    Kinashi, T., Inaba, K., Tsubata, T., Tashiro, K., Palacios, R. and Honjo, T. (1988): Differentiation of an interleukin 3-dependent precursor B cell clone into immunoglobulin-producing cells in vitro. Proc. Natl. Acad. Sci. USA. 85: 4473-4477.

    Kinashi, T., Inaba, K., Tsubata, T., Tashiro, K., Palacios, R. and Honjo, T. (1988): Differentiation of a precursor cell with the germline context of immunoglobulin gene into immunoglobulin-producing cells in vitro. Ann. N. Y. Acad. Sci. 546: 1-8.

    Tsubata, T., Kumagai, S., Imura, H., Nishikawa, S.-I. and Katsura, Y. (1987): Study of anti-DNA repertoire in normal and lupus mice. In "New Horizon of Animal Models for Autoimmune Diseases" (ed. by H. Wigzell and M. Kyogoku), pp.121-126, Academic Press, Tokyo.

    Katsura, Y., Kina, T., Amagai, T., Tsubata, T., Hirayoshi, K., Takaoki, Y., Sado, T. and Nishikawa, S.-I. (1986): Limiting dilution analysis of the stem cells for T cell lineage. J. Immunol. 137: 2434-2439.

    Kumagai, S., Namiuchi, S., Ozaki, S., Sano, H., Tsubata, T., Suginoshita, T. and Imura, H. (1985): Tac antigen-positive T cells activated in autologous mixed lymphocyte reaction regulate the generation of killer T cells against hapten-modified autologous cells. J. Immunol. 134: 711-719.