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Regulation of B lymphocyte activation by molecular interactions in glycocalyx

Research Project

Project/Area Number 18H02610
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionTokyo 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(Kenkyū-buntansha) 赤津 ちづる  東京医科歯科大学, 難治疾患研究所, 助教 (60735984)
王 継揚  東京医科歯科大学, 難治疾患研究所, 特任講師 (80231041)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
KeywordsGlycocalyx / レクチン / シスリガンド / Bリンパ球 / 免疫不全 / シグナル伝達 / シアル酸 / Siglec / CD22 / BCR / 糖鎖シスリガンド / チロシンホスファターゼ / Proximity labeling / 分化過程での制御 / CD72 / proximity labeling / CEACAM-1
Outline of Final Research Achievements

Glycans in glycoproteins and glycolipids on the cell surface form a layer rich in glycans called glycocalyx. In glycocalyx, lectins, proteins recognize specific glycans, interact with corresponding glycan ligands. In this study, we demonstrate that CD22, an inhibitory receptor and a sialic acid-binding lectin expressed in B lymphocytes, positively and negatively regulate BCR signaling by interacting with different sialic acid-containing ligands, thereby contributing to the quality control of B lymphocytes. This result suggests a crucial role of molecular interaction in glycocalyx in the regulation of cellular functions.

Academic Significance and Societal Importance of the Research Achievements

レクチンは種々の異なる糖タンパク質や糖脂質に結合し、その結合はタンパク質同士の結合に比べて弱い場合が多いため、レクチンの役割には不明な点が多い。本研究では、種々の新規ツールを駆使することで、レクチンの1つであるCD22とその糖鎖リガンドとの相互作用がどのようにCD22の機能を制御し、細胞機能を制御するかを明らかにした。このことで、レクチンと糖鎖の相互作用の重要性を明らかにするとともに、その解析法を進歩させた。また、CD22が免疫不全B細胞の機能を回復させることを明らかにしたことは、免疫不全症の新たな治療法の開発に結びつくと期待される。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (25 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (2 results)

  • [Int'l Joint Research] Stanford University/Duke University/UCSF(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Erlangen(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Alberta(カナダ)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] The inhibitory coreceptor CD22 restores B cell signaling by developmentally regulating <i> Cd45 <sup>?/?</sup> </i> immunodeficient B cells2022

    • Author(s)
      Akatsu Chizuru、Alborzian Deh Sheikh Amin、Matsubara Naoko、Takematsu Hiromu、Schweizer Astrid、Abdu-Allah Hajjaj H. M.、Tedder Thomas F.、Nitschke Lars、Ishida Hideharu、Tsubata Takeshi
    • Journal Title

      Science Signaling

      Volume: 15 Issue: 723 Pages: 723-723

    • DOI

      10.1126/scisignal.abf9570

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Role of inhibitory B cell co‐receptors in B cell self‐tolerance to non‐protein antigens*2022

    • Author(s)
      Tsubata Takeshi
    • Journal Title

      Immunological Reviews

      Volume: 307 Issue: 1 Pages: 53-65

    • DOI

      10.1111/imr.13059

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Protein Tyrosine Phosphatase SHP-1 (PTPN6) but Not CD45 (PTPRC) Is Essential for the Ligand-Mediated Regulation of CD22 in BCR-Ligated B Cells2021

    • Author(s)
      Alborzian Deh Sheikh Amin、Akatsu Chizuru、Abdu-Allah Hajjaj H. M.、Suganuma Yuki、Imamura Akihiro、Ando Hiromune、Takematsu Hiromu、Ishida Hideharu、Tsubata Takeshi
    • Journal Title

      The Journal of Immunology

      Volume: 206 Issue: 11 Pages: 2544-2551

    • DOI

      10.4049/jimmunol.2100109

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A CD22?Shp1 phosphatase axis controls integrin β7 display and B cell function in mucosal immunity2021

    • Author(s)
      Ballet Romain、Brennan Martin、Brandl Carolin、Feng Ningguo、Berri Jeremy、Cheng Julian、Oc?n Borja、Alborzian Deh Sheikh Amin、Marki Alex、Bi Yuhan、Abram Clare L.、Lowell Clifford A.、Tsubata Takeshi、Greenberg Harry B.、Macauley Matthew S.、Ley Klaus、Nitschke Lars、Butcher Eugene C.
    • Journal Title

      Nature Immunology

      Volume: 22 Issue: 3 Pages: 381-390

    • DOI

      10.1038/s41590-021-00862-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of Siglec Cis-Ligands by Proximity Labeling2020

    • Author(s)
      Alborzian Deh Sheikh Amin、Akatsu Chizuru、Tsubata Takeshi
    • Journal Title

      Methods in Molecular Biology

      Volume: 2132 Pages: 75-83

    • DOI

      10.1007/978-1-0716-0430-4_8

    • ISBN
      9781071604298, 9781071604304
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Inhibitory B cell co-receptors and autoimmune diseases.2019

    • Author(s)
      Tsubata, T
    • Journal Title

      Immunol. Med.

      Volume: 42 Pages: 108-116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Essential role of NADPH oxidase-dependent production of reactive oxygen species in maintenance of sustained B cell receptor signaling and B cell proliferation.2019

    • Author(s)
      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.
    • Journal Title

      J. Immunol.

      Volume: 202 Pages: 2546-2557

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD22-binding synthetic sialosides regulate B lymphocyte proliferation through CD22 ligand-dependent and independent pathways, and enhance antibody production in mice.2018

    • Author(s)
      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.
    • Journal Title

      Front. Immunol.

      Volume: 9 Pages: 820-820

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ligand recognition determines the role of inhibitory B cell co-receptors in the regulation of B cell homeostasis and autoimmunity.2018

    • Author(s)
      Tsubata, T.
    • Journal Title

      Front Immunol.

      Volume: 9 Pages: 2276-2276

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 抑制性B細胞共受容体 CD22(Siglec-2) による糖鎖依 存的な免疫不全B細胞の機能回復2021

    • Author(s)
      赤津ちづる、Alborzian-Deh-Sheikh Amin、鍔田武志.
    • Organizer
      第 94 回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The SHP-1-activating inhibitory co-receptor CD22 paradoxically augments BCR signaling in immunodeficient B cells.2020

    • Author(s)
      Chizuru Akatsu, Amin Alborzian Deh Sheikh and Takeshi Tsubata.
    • Organizer
      The 14th International Conference on Protein Phosphatase
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of anti-CD22 antibody that inhibits ligand binding of CD22.2019

    • Author(s)
      Long Wang、Endo Ayaka、Takematsu Hiromu、Fedder Thomas、Tsubata Takeshi.
    • Organizer
      The Regular Meeting of the Japanese Biochemical Society Kanto Branch
    • Related Report
      2019 Annual Research Report
  • [Presentation] 抑制性 B 細胞共受容体 CD72 による SLE 関連自己抗原への自己免疫応答の抑制2019

    • Author(s)
      赤津ちづる、遠藤萌恵、沼本修孝、Quan-Zhen Li、関根英治、藤田禎三、伊藤暢聡、鍔田武志 .
    • Organizer
      第 34 回自己免疫研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 内因性糖鎖リガンドによる CD22/Siglec-2 の機能制御.2019

    • Author(s)
      Amin Alborzian Deh Sheikh, 赤津ちづる、鍔田武志.
    • Organizer
      第 5 回糖鎖免疫研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The Inhibitory B Cell Co-Receptor CD72 Regulates Tolerance to Self Nucleic Acids Crucial for Development of Systemic Lupus Erythematosus.2018

    • Author(s)
      Takeshi Tsubata
    • Organizer
      Keystone Symposia, B cells: Mechanisms in Immunity and Autoimmunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The role of CD22 glycan cis-ligands in the regulation of B cell tonic signaling.2018

    • Author(s)
      Amin Alborzian Deh Sheikh, Chizuru Akatsu, Hideharu Ishida and Takeshi Tsubata.
    • Organizer
      The Regular Meeting of the Japanese Biochemical Society Kanto Branch
    • Related Report
      2018 Annual Research Report
  • [Presentation] The role of ligand recognition of SHP-1 activating receptor CD22 in the regulation of B cell tonic signaling.2018

    • Author(s)
      Amin Alborzian Deh Sheikh, Chizuru Akatsu, Hideharu Ishida and Takeshi Tsubata.
    • Organizer
      Workshop on Frontiers in Phosphatase Research and Drug Discovery (ICPP13)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ligand recognition determines functional properties of inhibitory B cell co-receptors.2018

    • Author(s)
      Takeshi Tsuabta.
    • Organizer
      International Symposium on B cells
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of CD72 in the regulation of autoantibody production and type 1 interferon production in autoimmune disease.2018

    • Author(s)
      Chizuru Akatsu, Quan-Zhen Li, and Takeshi Tsubata
    • Organizer
      The 47th Annual Meeting of the Japanese Society for Immunology
    • Related Report
      2018 Annual Research Report
  • [Presentation] CD22 の糖鎖リガンドは B 細胞抗原受容体 (BCR)の機能変化依存的に CD22 の BCR 抑制機能を制御する.2018

    • Author(s)
      赤津ちづる、Alborzian-Deh-Sheikh Amin、石田秀治、鍔田武志
    • Organizer
      第 91 回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Book] Identification of Siglec Cis-ligands by Proximity Labeling. In “Lectin Purification and Analysis: Methods and Protocols” ed. by Jun Hirabayashi2020

    • Author(s)
      Alborzian Deh Sheikh, A., Akatsu, C. and Tsubata, T.
    • Total Pages
      693
    • Publisher
      Springer
    • ISBN
      9781071604298
    • Related Report
      2019 Annual Research Report
  • [Book] Development of Siglec Regulators. In “Glycoscience: Basic Science to Applications” ed. by Naoyuki Taniguchi, Tamao Endo, Jun Hirabayashi, Shoko Nishihara, Kenji Kadomatsu, Kazunari Akiyoshi and Kiyoko F. Aoki-Kinoshita2019

    • Author(s)
      Tsubata, T
    • Total Pages
      405
    • Publisher
      Springer
    • ISBN
      9789811358562
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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