Carbohydrate recognition of B lymphocyte lectins and their function

• Project/Area Number: 23390063
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TSUBATA Takeshi 東京医科歯科大学, 難治疾患研究所, 教授 (80197756)
• Co-Investigator(Renkei-kenkyūsha): ITO Nobutoshi 東京医科歯科大学, 難治疾患研究所分子構造情報学分野, 教授 ; WATANABE Kozo 東京医科歯科大学, 難治疾患研究所免疫疾患分野, 助教 (20376718)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000); Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: Bリンパ球、 / レクチン / 糖鎖 / 抑制性受容体 / Bリンパ球 / 硫酸化糖鎖 / Ｓｍ／ＲＮＰ / CD72 / シグナル伝達 / 自己抗体 / Sm/RNP / ヘパリン / スルファチド

Outline of Final Research Achievements

CD72 is an inhibitory receptor expressed mostly in B lymphocytes, and contains a C-type lectin-like domain. We demonstrated that CD72 binds to various sulfated glycans and inhibits immune responses to sulfated glycans. Sulfated glycans are abundantly produced in vertebrates including human, but are not normally produced by microbes. These findings suggest that CD72 recognizes sulfated glycans as a self-associated molecular pattern, and is involved in distinction between self and microbes.

Research Products

• [Journal Article] FcμR interacts and cooperates with the B cell receptor to promote B cell survival (2015)
  • Author(s): Ouchida. R., Lu. Q., Liu. J., Li. Y., Chu. Y., Tsubata. T. and Wang, J.Y.
  • Journal Title: J. Immunol Volume: 194 Pages: 3096-3101
  • DOI: 10.4049/jimmunol.1402352
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Excess CD40L does not rescue anti-DNA B cells from clonal anergy. (2014)
  • Author(s): Kishi, Y., Higuchi, T., Phoon, S., Kamiya, K., Riemekasten, G., Akiyoshi, K., Weigert, M. and Tsubata, T.
  • Journal Title: F1000Research Volume: 109 Pages: 218-218
  • DOI: 10.1073/pnas.1204509109
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functional Evaluation of Activation-dependent Alteration of Sialoglycans in T Cells (2014)
  • Author(s): 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.
  • Journal Title: J.Bio.Chem. Volume: 289 Pages: 1564-1579
  • DOI: 10.1074/jbc.m113.523753
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] LAPTM5 promotes lysosomal degradation of intracellular CD3ζ but not of cell surface CD3ζ. (2014)
  • Author(s): Kawai, Y., Ouchida, R., Yamasaki, S., Dragone, L., Tsubata, T. and Wang, J.-Y.
  • Journal Title: Immunol Cell Biol. Volume: 92 Pages: 527-534
  • DOI: 10.1038/icb.2014.18
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction. (2013)
  • Author(s): Shimoda, M., Bolduc, A., Takezaki, M., Ametani, Y., Huang, L., Nutt S. L., Kamanaka, M., Flavell, R. A., Mellor A. L, Tsubata, T. andKoni, P.
  • Journal Title: J. Immunol. Volume: 190 Pages: 3189-3196
  • DOI: 10.4049/jimmunol.1203364
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cd72c is a modifier gene that regulates Faslpr-induced autoimmune disease. (2013)
  • Author(s): Xu, M., Hou, R., Sato-Hayashizaki, A., Man, R., Zhu, C., Wakabayashi, C, Hirose, S., Adachi, T. and Tsubata, T.
  • Journal Title: J. Immunol. Volume: 190 Pages: 5436-5445
  • DOI: 10.4049/jimmunol.1203576
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Excess CD40L does not rescue anti-DNA B cells from clonal anergy. (2013)
  • Author(s): Aslam, M., Kishi, Y. and Tsubata, T.
  • Journal Title: F1000 Research Volume: 2 Pages: 218-218
  • DOI: 10.12688/f1000research.2-218.v2
  • Peer Reviewed
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy. (2012)
  • Author(s): Klionsky, D.J., Abdalla, F. C. Tsubata, T. et al.
  • Journal Title: Autophagy Volume: 8 Pages: 1-100
  • Peer Reviewed
• [Journal Article] Role of inhibitory BCR co-receptors in immunity. (2012)
  • Author(s): Tsubata, T.
  • Journal Title: Infect Disord Drug Targets Volume: 12 Pages: 181-190
  • Peer Reviewed
• [Journal Article] Apoptotic volume decrease (AVD) is independent of mitochondrial dysfunction and initiator caspase activation. (2012)
  • Author(s): 前野恵美、鍔田武志、岡田泰伸
  • Journal Title: Cells Volume: 1 Pages: 1156-1167
  • DOI: 10.3390/cells1041156
  • Peer Reviewed
• [Journal Article] Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic resticulum. (2012)
  • Author(s): Hitomi Y, et al.
  • Journal Title: BMC Immunol. Volume: 13 Pages: 72-72
  • DOI: 10.1186/1471-2172-13-72
  • Peer Reviewed
• [Journal Article] CD22-antagonists with nanomolar potency: The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold. (2011)
  • Author(s): Abdu-Allah,H.H.M.,Takematsu,H., Kozutsumi, Y.,Tsubata, H., Ishida, H. and Kiso,M. et al.
  • Journal Title: Bioorg. Med. Chem. Volume: 19 Pages: 1966-1971
  • Peer Reviewed
• [Journal Article] The use of cationic nanogels to deliver proteins to myeloma cells and primary T lymphocytes that poorly express heparan sulfate. (2011)
  • Author(s): K.Watanabe, et al
  • Journal Title: Biomaterials Volume: 32 Pages: 5900-5905
  • DOI: 10.1016/j.biomaterials.2011.04.058
  • Peer Reviewed
• [Journal Article] Design and synthesis of multivalent heterobifunctional CD22-ligand as a potential immunomodulator. (2011)
  • Author(s): Abdu-Allah, H. H. M, Watanabe, K., Kanie, O., Tsubata, T. Ishida, H. and Kiso, M.
  • Journal Title: Synthesis Volume: 18 Pages: 2968-2974
  • Peer Reviewed
• [Journal Article] Amplified B lymphocyte CD40 signaling drives regulatory B10 cell expansion in mice. (2011)
  • Author(s): Poe, J. C., Smith , S. H., Haas, K. M., Yanabe, K., Tsubata, T., Matsushita, T. and Tedder, T. F.
  • Journal Title: PLoS ONE Volume: 6 Pages: 22464-22464
  • DOI: 10.1371/journal.pone.0022464
  • Peer Reviewed
• [Journal Article] High-affinity ligands of Siglec receptors and their therapeutic potentials. (2011)
  • Author(s): Magesh, S., Ando, H., Tsubata, T., Ishida, H. and Kiso, M.
  • Journal Title: Current Medicinal Chemistry Volume: 18 Pages: 3537-3550
  • Peer Reviewed
• [Presentation] 糖鎖抗原への免疫応答・不応答のメカニズム (2015)
  • Author(s): 鍔田武志
  • Organizer: 共同研究拠点研究集会 Glyco Immunology 2014.
  • Place of Presentation: 東京医科歯科大学、東京
  • Year and Date: 2015-02-17 – 2015-02-18
  • Invited
• [Presentation] A mouse model for chronic inflammatory diseases spontaneously develops CD4/CD8 double-positive T cell leukemia/lymphoma. (2015)
  • Author(s): P. A. Koni., Ren, M., Tsubata, T., Khleif, S., Maverakis, E. and Shimoda, M.
  • Organizer: The 54th Midwinter Conference of Immunologists at Asilomar.
  • Place of Presentation: Big Bear Lake, California (USA)
  • Year and Date: 2015-01-24 – 2015-01-25
  • Invited
• [Presentation] Bリンパ球に発現するCD22/Siglec-2を標的とした免疫増強化合物の開発 (2015)
  • Author(s): 鍔田武志
  • Organizer: 第8回次世代アジュバント研究会
  • Place of Presentation: 千里ライフサイエンスセンター、大阪
  • Year and Date: 2015-01-20
  • Invited
• [Presentation] CD22-binding synthetic sialosides as a tool to elucidate the role of CD22 cis-ligand and as a novel immunostimulan. (2014)
  • Author(s): Tsubata, T.
  • Organizer: Medical Research Institute 40th Anniversary, 13th Surugadai International Symposium & Joint Usage/Research Program of Medical Research Institute International Symposium.
  • Place of Presentation: Tokyou Medical and Dental Univ. Ｔｏｋｙｏ, Japan
  • Year and Date: 2014-11-28
  • Invited
• [Presentation] Role of CD22/Siglec2 and its ligand in B lymphocyte activation. (2014)
  • Author(s): Tsubata, T.
  • Organizer: Joint annual meeting of SFG &JSCR, Integrating Glycoscience from Biology and Chemistry to Medicine.
  • Place of Presentation: Hilton Hawaiian Village, Honolulu, Hawaii (USA)
  • Year and Date: 2014-11-16 – 2014-11-19
  • Invited
• [Presentation] Synthetic sialosides that regulate CD22/Siglec-2, a B lymphocyte membrane molecule activating SH2-containing phosphatases. (2014)
  • Author(s): Tsubata, T.
  • Organizer: 11th International Conference on Protein Phosphatase
  • Place of Presentation: Tohoku Univ. Sendai, Japan
  • Year and Date: 2014-11-12 – 2014-11-14
  • Invited
• [Presentation] 免疫グロブリンの機能多様性と疾患 (2014)
  • Author(s): 鍔田武志
  • Organizer: 第三回高齢者ネフローゼ症候群治療研究会・講演会
  • Place of Presentation: ＫＰＰ八重洲ビル、東京
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] 近畿圏を中心としたリウマチ膠原病専門医 (2014)
  • Author(s): 鍔田武志
  • Organizer: 臨床免疫セミナー
  • Place of Presentation: ウエスティン都ホテル、京都
  • Year and Date: 2014-10-04
  • Invited
• [Presentation] Bリンパ球の活性化制御と自己免疫 (2014)
  • Author(s): 鍔田武志
  • Organizer: 第２３回日本シェーグレン症候群学会学術集会
  • Place of Presentation: ホテルニュー長崎、長崎
  • Year and Date: 2014-09-12 – 2014-09-13
  • Invited
• [Presentation] 自己反応性Bリンパ球の制御と細胞死 (2014)
  • Author(s): 鍔田武志
  • Organizer: 第23回日本Cell Deth学会学術集会
  • Place of Presentation: 東京医科歯科大学、東京
  • Year and Date: 2014-07-18 – 2014-07-19
  • Invited
• [Presentation] SHP-1-activating Receptors in B lymphocytes. (2013)
  • Author(s): Tsubata, T.
  • Organizer: The 2nd Taiwan-Japan Bilateral Conference on Protein Phosphatase
  • Place of Presentation: NHRI, Hsinchu, Taiwan.
  • Year and Date: 2013-11-27 – 2013-11-29
  • Invited
• [Presentation] Sialic acids and immune responses. (2013)
  • Author(s): Tsubata, T.
  • Organizer: Molecular Frontier Science Conference for Humboltians and DAAD Alumni
  • Place of Presentation: East China Univ., Shanghai, China
  • Year and Date: 2013-09-20 – 2013-09-22
  • Invited
• [Presentation] CD72cはFas欠損マウスでの自己免疫疾患発症を制御する修飾遺伝子である (2013)
  • Author(s): 鍔田武志
  • Organizer: 第22回日本cell deth 学会学術集会
  • Place of Presentation: Kyoto Univ., Kyoto
  • Year and Date: 2013-07-19
  • Invited
• [Presentation] CD72C , a hapolotype encoding the SHP-1-binding B lymphocyte molecule, is a modifier gene for murine lupus (2013)
  • Author(s): Tsubata, T.
  • Organizer: the 10th International Conference on Protein Phosphatase
  • Place of Presentation: Tokyo
  • Invited
• [Presentation] 自己抗体産生とアイソタイプ (2013)
  • Author(s): 鍔田武志
  • Organizer: 第20回自己抗体と自己免疫シンポジウム
  • Place of Presentation: 東京
  • Invited
• [Presentation] Excess B cell CD40/CD40L signaling promotes CD4 T cell-mediated encephalomyelitis in mice. (2013)
  • Author(s): himoda. M., Bolduc. A., Takezaki. M., Tsubata. T. and Koni. P-A.
  • Organizer: Immunology 2013 AAI Annual meeting.
  • Place of Presentation: Honolulu, U.S.A.
• [Presentation] Unconventional B cell antigen receptor endocytosis pathway. (2013)
  • Author(s): Takata. T., Tang. M. and Tsubata. T.
  • Organizer: Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] Cd72c is a modifier gene that regulates Faslpr-induced autoimmune disease. (2013)
  • Author(s): Xu. M., Hou. R., Sato-Hayashizaki. A., Man. R-Y., Zhu. C., Wakabayashi. C., Hirose. S., Adachi. T. and Tsubata. T.
  • Organizer: Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] Distinct tolerance mechanisms for anti-DNA and anti-Sm B cells. (2013)
  • Author(s): Mohammad. A. and Tsubata T.
  • Organizer: Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] Glia maturation factor-γ regulates marginal zone B cell migration and humoral immune responses. (2013)
  • Author(s): Li. Y., Hase. K., Tsubata. T. and Wang. J-Y.
  • Organizer: Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] Identification of a putative form of AID that inhibits Ig gene hypermutation. (2013)
  • Author(s): Kano. C., Ohno. H., Tsubata. T. and Wang. J-Y.
  • Organizer: Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] Replenishment of long-live plasma cellsis constitutively restrictedby CD4+ T cells in the ir maintenance phase after influenza vaccination. (2013)
  • Author(s): Onodera. T., Takahashi. Y., Adachi. T., Tsubata. T., Kurosaki. T. and Ato. M.
  • Organizer: Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] CD72の構造解析に向けて (2013)
  • Author(s): 品川健朗、沼本修孝、鍔田武志、伊藤暢聡
  • Organizer: 第51回日本生物物理学会年会
  • Place of Presentation: 京都
• [Presentation] Synthesis and biological evaluation of the mimics of cis ligand for CD22 (2012)
  • Author(s): Suganuma, Y., Matsubara, N., Iwayama, Y., Ueki, A., Imamura, A., Ando, H., Tsubata, T., Ishida, H. and Kiso, M.
  • Organizer: The 4th Asian Communication for Glycobiology and Glycotechnology (ACGG)
  • Place of Presentation: Jeju, Korea
• [Presentation] シグレックと感染免疫 (2012)
  • Author(s): 鍔田武志
  • Organizer: ５回感染病態研究フロンティア
  • Place of Presentation: 東京
  • Invited
• [Presentation] 全身性自己免疫疾患と自己トレランス (2012)
  • Author(s): 鍔田武志
  • Organizer: 第四回全国共同利用・共同研究「酵素学研究拠点」シンポジウム
  • Place of Presentation: 東京
  • Invited
• [Presentation] Ｃ型レクチン様分子CD72による硫酸糖鎖への免疫応答の制御 (2012)
  • Author(s): 鍔田武志
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Time, place and pathway-specific involvement of reactive oxygen species in B cell antigen receptor signaling. (2012)
  • Author(s): Tang, M., Takata, T., Tsubata, T.
  • Organizer: Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe
• [Presentation] Excess CD40L specifically perturbs self-tolerance of anti-Sm antibody recognizing the same components as patient-derived antibodies. (2012)
  • Author(s): Kishi, Y., Phoon., S., Tsubata, T.
  • Organizer: Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kobe
• [Presentation] Time, place and pathway-specific involvement of reactive oxygen species in B cell antigen receptor signaling. (2012)
  • Author(s): Tang, M., Takata, T., Tsubata, T.
  • Organizer: .日本免疫学会学術総会
  • Place of Presentation: 神戸
• [Presentation] Excess CD40L specifically perturbs self-tolerance of anti-Sm antibody recognizing the same components as patient-derived antibodies. (2012)
  • Author(s): Kishi, Y., Phoon., S., Tsubata, T.
  • Organizer: .日本免疫学会学術総会
  • Place of Presentation: 神戸
• [Presentation] チロシンフォスファターゼSHP－１を活性化するＢリンパ球膜分子CD72の多型と自己免疫 (2012)
  • Author(s): 鍔田武志
  • Organizer: 第5回日本プロティンホスファターゼ研究会学術集会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] 辺緑帯Ｂリンパ球のアポトーシスと自己免疫 (2011)
  • Author(s): 鍔田武志
  • Organizer: 第20回日本Cell Deth学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] The C-type lectin-like domain containing B lymphocyte membrane molecule CD72 shows Ca2 ＋-independent lectin activity to sulfated glycans (2011)
  • Author(s): 渡辺幸造、安達貴弘、鍔田武志
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] Apoptotic marginal zone deletion of anti-Sm/RNP B cells is reversed by excess CD40L (2011)
  • Author(s): 岸祐介、鍔田武志
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] Role of Reactive Oxygen Species in B Cell Antigen Receptor Signaling (2011)
  • Author(s): Tang Miao、高田俊太朗、鍔田武志
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Book] 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).. (2014)
  • Author(s): Tsubata, T.
  • Total Pages: 400
  • Publisher: Springer-Verlag Berlin Heidelberg