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Regulation of lymphocyte cell division and oncogenesis

Research Project

Project/Area Number 18H02669
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionHiroshima University (2019-2020)
Kyushu University (2018)

Principal Investigator

YASUDA TOMOHARU  広島大学, 医系科学研究科(医), 教授 (40334429)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
KeywordsB細胞 / リンパ腫 / 細胞分裂 / 細胞老化 / 免疫応答 / 体細胞変異 / T細胞
Outline of Final Research Achievements

The cell division of immune cells not only amplify antigen-specific clones but also determine the direction of differentiation, that is critical for determining how immunity work. Immune cells that respond to the antigen must be arrested at the appropriate time after the onset of division, but the regulatory mechanism is unclear. The Cdkn2a gene was identified by the combination of transcriptome and proteome for the molecular basis that controls the growth limit of lymphocytes. Among the proteins encoded by the Cdkn2a gene, we found that there was a correlation between the B cell proliferation limit and the Arf expression. In addition to Arf, we were able to identify new factors that epigenetically controling B cell proliferation limit. B cell-specific knockout mouse of candidate gene was generated, and analysis of the effects on germinal center B cell response duration and immune response has been performed.

Academic Significance and Societal Importance of the Research Achievements

リンパ球は病原体など異物を認識すると増殖を開始し、それらが抗体産生細胞、細胞傷害性細胞、長期記憶細胞など多岐に役割の異なる細胞に分化し、即時あるいは生涯に渡る感染防御に寄与する。免疫細胞の分裂増殖は抗原特異的なクローンを増幅するだけでなく分化方向の決定とも連動することが知られており、免疫特性を決定する重要なファクターである。リンパ球の増殖が適切に制御されない状態、つまり増殖不応答状態では免疫不全につながり、逆に増殖が過度に亢進した状態では自己免疫疾患、リンパ増殖性疾患、リンパ腫発症などにつながるため、本研究の推進によりそれら疾患の克服に貢献する。

Report

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

    (20 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results)

  • [Int'l Joint Research] Max Delbruck Center(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Max Delbruck Center(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Max Delbruck Center(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] The FIRC Institute of Molecular Oncology(イタリア)

    • Related Report
      2018 Annual Research Report
  • [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] Pathologically Relevant Mouse Models for Epstein-Barr Virus-Associated B Cell Lymphoma2021

    • Author(s)
      Huang Shiyu、Yasuda Tomoharu
    • Journal Title

      Frontiers in Immunology

      Volume: 12

    • DOI

      10.3389/fimmu.2021.639844

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A conserved PI(4,5)P2-binding domain is critical for immune regulatory function of DOCK82021

    • Author(s)
      Sakurai Tetsuya、Kukimoto-Niino Mutsuko、Kunimura Kazufumi、Yamane Nana、Sakata Daiji、Aihara Ryosuke、Yasuda Tomoharu、Yokoyama Shigeyuki、Shirouzu Mikako、Fukui Yoshinori、Uruno Takehito
    • Journal Title

      Life Science Alliance

      Volume: 4 Issue: 4 Pages: e202000873-e202000873

    • DOI

      10.26508/lsa.202000873

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis2020

    • Author(s)
      Sommermann Thomas、Yasuda Tomoharu、Ronen Jonathan、Wirtz Tristan、Weber Timm、Sack Ulrike、Caeser Rebecca、Zhang Jingwei、Li Xun、Chu Van Trung、Jauch Anna、Unger Kristian、Hodson Daniel J.、Akalin Altuna、Rajewsky Klaus
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 25 Pages: 14421-14432

    • DOI

      10.1073/pnas.1921139117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Measuring protein synthesis during cell cycle by Azidohomoalanine (AHA) labeling and flow cytometric analysis.2019

    • Author(s)
      Imami K, Yasuda T.
    • Journal Title

      Bio-Protocol

      Volume: 1 Issue: 8 Pages: 1-7

    • DOI

      10.21769/bioprotoc.3215

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Measuring Protein Synthesis during Cell Cycle by Azidohomoalanine (AHA) Labeling and Flow Cytometric Analysis.2019

    • Author(s)
      Imami, K., Yasuda T.
    • Journal Title

      Bio-protocol

      Volume: 9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphorylation of the Ribosomal Protein RPL12/uL11 Affects Translation during Mitosis2018

    • Author(s)
      Imami Koshi、Milek Miha、Bogdanow Boris、Yasuda Tomoharu、Kastelic Nicolai、Zauber Henrik、Ishihama Yasushi、Landthaler Markus、Selbach Matthias
    • Journal Title

      Molecular Cell

      Volume: 72 Issue: 1 Pages: 84-98

    • DOI

      10.1016/j.molcel.2018.08.019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 抗原受容体と免疫細胞の維持機構2020

    • Author(s)
      保田朋波流
    • Organizer
      第一三共 消化器疾患セミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 抗原受容体と免疫寿命のコントロール2020

    • Author(s)
      保田朋波流
    • Organizer
      広島市医師会 第135回学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] B cell division in the heterogeneous pre-tumor microenvironment is required for lymphoma development2020

    • Author(s)
      Tomoharu Yasuda, Klaus Rajewsky
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] EBウイルスとヒト免疫系の共生/共進化2019

    • Author(s)
      保田朋波流
    • Organizer
      中国四国ウイルス研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] EBV-LMP1による宿主抗原性転換と細胞傷害性T細胞分化2019

    • Author(s)
      保田朋波流
    • Organizer
      第1回 感染に起因する腫瘍の共同研究セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 広島市 抗原受容体とB細胞寿命2019

    • Author(s)
      保田朋波流
    • Organizer
      第65回 広島大学第二外科同門研修会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 抗原受容体シグナルとB細胞寿命2019

    • Author(s)
      保田朋波流
    • Organizer
      第46回 広島大学健康長寿研究拠点HiHAセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] EBウイルスとヒト免疫系の共生/共進化2019

    • Author(s)
      保田朋波流
    • Organizer
      広島免疫学リサーチセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Active B cell division on plasma cell niche is required for lymphoma development.2018

    • Author(s)
      Yasuda, T., Baba, Y., and Rajewsky, K.
    • Organizer
      The 13th International Symposium of the Institute Network for Biomedical Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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