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Mechanisms underlying long-term survival and immune-modulatory function of plasma cells

Research Project

Project/Area Number 20H03503
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionOsaka University

Principal Investigator

ISE Wataru  大阪大学, 感染症総合教育研究拠点, 教授 (70323483)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords抗体 / プラズマ細胞 / 長期生存 / インテグリン / 生存
Outline of Research at the Start

プラズマ細胞から産生される抗体はウイルスや細菌の排除に必要不可欠である。プラズマ細胞の一部は骨髄などで長期に渡って生存し、抗体を産生し続けることから、プラズマ細胞の生存を支える分子基盤を明らかにすることはワクチン開発やアレルギー、自己免疫疾患の治療法開発にも重要である。申請者は長期生存プラズマ細胞を特異的に蛍光ラベルし、追跡・分離できる新たな実験系の樹立に成功した。本研究ではこの実験系を用いて、長期生存プラズマ細胞のマーカーの同定、生存制御機構の解明、そして抗体クラス特異的生存機構や局在の生理的意義の解明を試みる。

Outline of Final Research Achievements

We analyzed long-term survival of plasma cells in bone marrow, spleen, or gut by using plasma cell fate mapping system. We found that plasma cells survive in bone marrow better than in other tissues with isotype-dependent half-lives. Furthermore, we demonstrated that long-lived plasma cells are B220loMHC-IIlo and are immobilized in the BM environment. Unexpectedly, there was no significant difference in the longevity between pre-GC and post-GC plasma cells. Finally, we analyzed molecular mechanisms by which plasma cells generated in lymphoid tissues migrate to bone marrow and found that the transcription factor KLF2 is required for integrin beta 7 positive plasma cells to migrate to bone marrow.

Academic Significance and Societal Importance of the Research Achievements

プラズマ細胞の長期生存を支える分子機構を解明することは、ワクチン開発のみならず、アレルギーや自己免疫疾患の治療法開発にも重要である。本研究ではプラズマ細胞の生存ニッチとしての骨髄の重要性を確認すると同時に、長寿命プラズマ細胞の骨髄移動の分子メカニズムを初めて明らかにした。また長寿命プラズマ細胞を識別可能なマーカーの同定にも成功した。本研究の成果は、抗体産生応答の持続性に優れたワクチン開発に大きく貢献するものである。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (11 results)

All 2023 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (2 results) (of which Invited: 2 results) Book (1 results)

  • [Journal Article] Progressive differentiation toward the long-lived plasma cell compartment in the bone marrow.2023

    • Author(s)
      Koike T, Fujii K, Kometani K, Butler NS, Funakoshi K, Yari S, Kikuta J, Ishii M, Kurosaki T, Ise W
    • Journal Title

      Journal of Experimental Medicine

      Volume: 220 Issue: 2 Pages: 2-2

    • DOI

      10.1084/jem.20221717

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors2022

    • Author(s)
      Itahashi Kota、Irie Takuma、Yuda Junichiro、Kumagai Shogo、Tanegashima Tokiyoshi、Lin Yi-Tzu、Watanabe Sho、Goto Yasushi、Suzuki Jun、Aokage Keiju、Tsuboi Masahiro、Minami Yosuke、Ishii Genichiro、Ohe Yuichiro、Ise Wataru、Kurosaki Tomohiro、Suzuki Yutaka、Koyama Shohei、Nishikawa Hiroyoshi
    • Journal Title

      Science Immunology

      Volume: 7 Issue: 76 Pages: 1-20

    • DOI

      10.1126/sciimmunol.abk0957

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Batf-mediated epigenetic control of effector CD8 <sup>+</sup> T cell differentiation2022

    • Author(s)
      Tsao Hsiao-Wei、Kaminski James、Kurachi Makoto、Barnitz R. Anthony、DiIorio Michael A.、LaFleur Martin W.、Ise Wataru、Kurosaki Tomohiro、Wherry E. John、Haining W. Nicholas、Yosef Nir
    • Journal Title

      Science Immunology

      Volume: 7 Issue: 68

    • DOI

      10.1126/sciimmunol.abi4919

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Plasma cell generation during T-cell-dependent immune responses2021

    • Author(s)
      Ise Wataru、Kurosaki Tomohiro
    • Journal Title

      International Immunology

      Volume: 33 Issue: 12 Pages: 797-801

    • DOI

      10.1093/intimm/dxab071

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Silencing and activating anergic B cells2021

    • Author(s)
      Shinya Tanaka, Wataru Ise, Yoshihiro Baba, Tomohiro Kurosaki
    • Journal Title

      Immunological reviews

      Volume: 307 Issue: 1 Pages: 43-52

    • DOI

      10.1111/imr.13053

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] B cell-intrinsic TBK1 is essential for germinal center formation during infection and vaccination in mice2021

    • Author(s)
      Lee MSL, Inoue T, Ise W, Matsuo-Dapaah J, Wing JB, Temizoz B, Kobiyama K, Hayashi T, Patil A, Sakaguchi S, Simon AK, Bezbradica JS, Nagatoishi S, Tsumoto K, Inoue J, Akira S, Kurosaki T, Ishii KJ, Coban C
    • Journal Title

      Journal of Experimental Medicine

      Volume: 219 Issue: 2

    • DOI

      10.1084/jem.20211336

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] Tet DNA demethylase is required for plasma cell differentiation by controlling expression levels of IRF42020

    • Author(s)
      Fujii, K. Tanaka, S. Hasegawa, T. Narazaki, M. Kumanogoh, A. Koseki, H. Kurosaki, T. Ise, W.
    • Journal Title

      International Immunology

      Volume: 32 Issue: 10 Pages: 683-690

    • DOI

      10.1093/intimm/dxaa042

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 長寿命プラズマ細胞の分化と生存の制御2023

    • Author(s)
      伊勢 渉
    • Organizer
      第7回日本骨免疫学会 冬期学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] B細胞に発現するTet2/Tet3による全身性自己免疫寛容の制御2021

    • Author(s)
      伊勢渉
    • Organizer
      第65回日本リウマチ学会総会・学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Book] 食品免疫学事典2021

    • Author(s)
      日本食品免疫学会
    • Total Pages
      492
    • Publisher
      朝倉書店
    • ISBN
      9784254431261
    • Related Report
      2021 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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