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New insights on Clinical potential of IgM antibodies in transplantation

Research Project

Project/Area Number 20K09525
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Matsuda Yoshiko  国立研究開発法人国立成育医療研究センター, RI管理室, リサーチアソシエイト (90790303)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords制御性B細胞 / IgMメモリーB細胞 / Transitional B細胞 / B細胞レセプター / Tool-like receptor 9 / IL-10 / CpG-ODN / 免疫寛容 / Transitional B cell / Tool-like receptor9 / 腎臓移植 / 抗体関連型拒絶反応 / IgM型メモリーB細胞 / IgG型メモリーB細胞 / インビトロ アッセイ系 / IgM DSA / IgG DSA / 免疫制御 / B-1細胞 / B-2細胞 / IgM抗体 / ドナーHLA抗原 / in vitroアッセイ系 / 抗体関聯型拒絶反応 / 液性免疫 / B-2細胞 / IgMメモリ-B細胞 / 臓器移植 / IgM自然抗体 / 抗原高親和性IgM抗体
Outline of Research at the Start

臓器移植分野においては主にIgG抗体に臨床的意義が認められてきた。一方でIgM抗体においては一致した見解を認めていない。我々はin vitro末梢血単核球培養上清中のIgM抗体に着目することで特定の抗原に対する液性免疫反応の賦活化を予測可能なこと,培養上清中からは抗原に対して高親和性を有するIgM抗体が主に検出されることを明らかにした。よって本研究ではIgM抗体を産生細胞起源(B-1細胞,B-2細胞)などの違いも考慮した上でABMRへの関与方法を明らかにする。またIgM抗体を対象とした、薬剤感受性試験なども行い、新規のABMR治療法の開発につなげていく。

Outline of Final Research Achievements

Using an in vitro assay system that can induce memory B cells to differentiate into antibody-producing cells, we found that the level of activation of the antigen-antibody reaction can be evaluated in detail by evaluating IgM and IgG type donor-specific HLA antibodies together in the culture supernatant, and that transplanted grafts are protected from antigen-antibody reaction in cases in which IgM antibodies are produced. We found that IgM memory B cells have an immunosuppressive function and may be involved in the pathogenesis and suppression of B cell mediated disease.

Academic Significance and Societal Importance of the Research Achievements

B細胞分画ごとの免疫抑制機能を評価することで、臓器移植における抗体関連型拒絶反応を含む、B cell mediated diseaseにおける、病態改善や発症抑制に有用な分画が同定できた。またIgM -BCR stimulationとTLR9 signalingの組み合わせがこれらの分画の生存、分化を調節していることが明らかとなったため、免疫抑制機能を有するB細胞分画の生存、分化の誘導に応用できる可能性が示唆された。今後、従来の免疫抑制療法に代わり、臓器移植分野における免疫寛容誘導などへの治療応用も期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells2021

    • Author(s)
      Matsuda Yoshiko、Watanabe Takeshi、Li Xiao-Kang
    • Journal Title

      Frontiers in Immunology

      Volume: 12

    • DOI

      10.3389/fimmu.2021.682334

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of Immunoglobulin M-Type Donor-Specific Human Leukocyte Antigen-Antibody Levels in Supernatants from Cultured Peripheral Blood Mononuclear Cells as Predictors of Antibody-Mediated Rejection.2020

    • Author(s)
      Ryoichi Imamura, Yoshiko Matsuda, Koichi Tsutahara,Norio Nonomura, Shiro Takahara
    • Journal Title

      Pathogens

      Volume: 9 (9) Issue: 9 Pages: 733-733

    • DOI

      10.3390/pathogens9090733

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics of Immunoglobulin M Type Antibodies of Different Origins from the Immunologic and Clinical Viewpoints and Their Application in Controlling Antibody-Mediated Allograft Rejection2020

    • Author(s)
      Yoshiko Matsuda, Takahisa Hiramitsu, Xiao-Kang Li, Takeshi Watanabe
    • Journal Title

      Pathogens

      Volume: 10(1) Issue: 1 Pages: 4-4

    • DOI

      10.3390/pathogens10010004

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Comparison Of Igg And Igm Type B Cell Receptor-mediated Mtor Phosphorylation Signal2022

    • Author(s)
      松田 佳子
    • Organizer
      American Transplant congress
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] New evelorimus administration targeting the prevention of the development of antibody-mediated rejection considering the comparison of growth and survival in IgG and IgM memory B cells2020

    • Author(s)
      Yoshiko Matsuda, Hiroyuki Tezuka, Ryoichi Imamura, Shiro Takahara
    • Organizer
      American transplant congress
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2025-01-30  

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