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Elucidation of pathological significance of IgG4 using a novel mouse model

Research Project

Project/Area Number 19K22537
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionKyushu University

Principal Investigator

Baba Yoshihiro  九州大学, 生体防御医学研究所, 教授 (20415269)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsIgG4 / B細胞
Outline of Research at the Start

IgG4関連疾患は様々な臓器の肥厚性病変を認める全身性疾患であり、血中IgG4の高値と、罹患部のIgG4陽性プラズマ細胞の浸潤および線維化を特徴とする。自己免疫機序の関与が想定されているが、未だに原因は不明であり、疾患発症機序の解明と新規治療法の開発が急がれる。本研究では、新規マウスモデルを樹立し、免疫グロブリンIgG4産生B細胞の応答とIgG4抗体の疾患への関与を解明することにより、IgG4関連疾患およびアレルギー疾患病態の理解を目指す。

Outline of Final Research Achievements

IgG4-related disease is characterized by high blood IgG4 antibody levels and fibrosis. In addition, IgG4 has been shown to suppress allergies. Although the relationship between IgG4 and allergic diseases is suspected, the details are unknown. A major reason for the lack of progress in IgG4 research is the absence of IgG4 in mice. Therefore, we gnerated a new mouse that produces human IgG4. We showed that B cell differentiation of this mouse was normal. In addition, IgG4 production was observed by immunization. Thus, the newly created IgG4-producing mouse may be a useful tool for verifying the role of IgG4 in vivo.

Academic Significance and Societal Importance of the Research Achievements

本研究で作成した新規ヒトIgG4産生マウスは、これまで不可能だったIgG4陽性B細胞のin vivoでの活性化や分化、ならびにIgG4抗体の疾患制御の役割を検証することが可能となり、IgG4の病理的意義を直接的に調べることができる。よって、IgG4関連疾患およびアレルギー疾患の理解と予測、さらには、治療の選択に貢献できると考えられる。また、謎の多いIgG4の機能という、基礎免疫学の研究領域の発展に大きく貢献することが期待される。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (9 results) (of which Invited: 6 results) Book (1 results)

  • [Journal Article] Generation and characterization of CD19-iCre mice as a tool for efficient and specific conditional gene targeting in B cells.2021

    • Author(s)
      Yasuda T, Saito Y, Ono C, Kawata K, Baba A, Baba Y.
    • Journal Title

      Sci. Rep.

      Volume: 11 Issue: 1 Pages: 5524-5524

    • DOI

      10.1038/s41598-021-84786-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity2020

    • Author(s)
      Tanaka, S. Ise, W. Inoue, T. Ito, A. Ono, C. Shima, Y. Sakakibara, S. Nakayama, M. Fujii, K. Miura, I. Sharif, J. Koseki, H. Koni, P. A. Raman, I. Li, Q. Z. Kubo, M. Fujiki, K. Nakato, R. Shirahige, K. Araki, H. Miura, F. Ito, T. Kawakami, E. Baba, Y. Kurosaki, T.
    • Journal Title

      Nature Immunology

      Volume: 21 Issue: 8 Pages: 950-961

    • DOI

      10.1038/s41590-020-0700-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes2020

    • Author(s)
      Sakaguchi Taiki、Okumura Ryu、Ono Chisato、Okuzaki Daisuke、Kawai Takafumi、Okochi Yoshifumi、Tanimura Natsuko、Murakami Mari、Kayama Hisako、Umemoto Eiji、Kioka Hidetaka、Ohtani Tomohito、Sakata Yasushi、Miyake Kensuke、Okamura Yasushi、Baba Yoshihiro、Takeda Kiyoshi
    • Journal Title

      Cell Reports

      Volume: 31 Issue: 10 Pages: 107755-107755

    • DOI

      10.1016/j.celrep.2020.107755

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] B Cell Receptor Signaling.2020

    • Author(s)
      Tanaka S, Baba Y.
    • Journal Title

      Adv. Exp. Med. Biol.

      Volume: 1254 Pages: 23-36

    • DOI

      10.1007/978-981-15-3532-1_2

    • ISBN
      9789811535314, 9789811535321
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Heterogeneous subsets of B-lineage regulatory cells (Breg cells).2020

    • Author(s)
      Baba Y, Saito Y, Kotetsu Y.
    • Journal Title

      Int. Immunol.

      Volume: 32 Issue: 3 Pages: 155-16

    • DOI

      10.1093/intimm/dxz068

    • Related Report
      2020 Annual Research Report
  • [Journal Article] GPR40 activation initiates store-operated Ca2+ entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells2019

    • Author(s)
      Usui R, Yabe D, Fauzi M, Goto H, Botagarova A, Tokumoto S, Tatsuoka H, Tahara Y, Kobayashi S, Manebe T, Baba Y, Kurosaki T, Herrera PL, Ogura M, Nagashima K, Inagaki N
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 15562-15562

    • DOI

      10.1038/s41598-019-52048-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors2019

    • Author(s)
      Nakai Akiko、Fujimoto Jun、Miyata Haruhiko、Stumm Ralf、Narazaki Masashi、Schulz Stefan、Baba Yoshihiro、Kumanogoh Atsushi、Suzuki Kazuhiro
    • Journal Title

      Journal of Experimental Medicine

      Volume: 216 Issue: 7 Pages: 1630-1647

    • DOI

      10.1084/jem.20181494

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] THE ROLL OF B CELLS IN ALLERGY2019

    • Author(s)
      齋藤雄一、馬場義裕
    • Journal Title

      Japanese Journal of Allergology

      Volume: 68 Issue: 6 Pages: 661-667

    • DOI

      10.15036/arerugi.68.661

    • NAID

      130007678533

    • ISSN
      0021-4884, 1347-7935
    • Related Report
      2019 Research-status Report
  • [Presentation] B細胞の免疫応答制御機構2020

    • Author(s)
      馬場義裕
    • Organizer
      第16回皮膚免疫疾患研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] B細胞による自己免疫疾患制御2020

    • Author(s)
      馬場義裕
    • Organizer
      免疫と神経疾患オンラインセミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] B細胞はどのようにして免疫応答を制御するのか2019

    • Author(s)
      馬場義裕
    • Organizer
      第93回染色体工学研究センターセミナー
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] B細胞の免疫応答制御機構2019

    • Author(s)
      馬場義裕
    • Organizer
      がん免疫セミナー(千葉)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] B細胞の免疫応答制御機構2019

    • Author(s)
      馬場義裕
    • Organizer
      がん免疫セミナー(東京)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 第18回レジェンドセミナー2019

    • Author(s)
      馬場義裕
    • Organizer
      免疫反応を抑制するB細胞
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Role of Fcrl5 in B cell immune response and peripheral tolerance.2019

    • Author(s)
      Ono C, Kochi Y, Tanaka S, Yamamoto K, Baba Y.
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Ten-eleven translocaion (Tet) in B cells prevent autoimmunity.2019

    • Author(s)
      Tanaka S, Ise W, Kurosaki T, Baba Y
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of IL-17A+ Vγ6 γδ T cells in mouse thymus.2019

    • Author(s)
      Hatano S, Tun X, Matsumoto M, Baba Y, Yoshikai Y.
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Book] 「B細胞分化」標準免疫学2021

    • Author(s)
      馬場義裕
    • Total Pages
      9
    • Publisher
      医学書院
    • ISBN
      9784260042383
    • Related Report
      2020 Annual Research Report

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Published: 2019-07-04   Modified: 2022-01-27  

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