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Molecular mechanisms underlying selection and maintenance of high affinity plasma cells

Research Project

Project/Area Number 17K08883
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Immunology
Research InstitutionOsaka University

Principal Investigator

Ise Wataru  大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (70323483)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords抗体 / プラズマ細胞 / 胚中心 / 転写因子 / B細胞 / DNAメチル化 / Tet / IRF4 / 免疫学
Outline of Final Research Achievements

1) We identified plasma cell precursors (Bcl6loIRF4hiCD69hi cells) in germinal center (GC). The generation of these cells requires strong help from T cells via CD40 and sustained interaction with T cells. Fate mapping of GC B cells revealed that in contrast to memory B cells, plasma cells are generated from early to late GCs continuously.
2) We demonstrated that DNA demethylase Tet2 and Tet3 are required for plasma cell generation. Tet2/3-deficient B cells were not able to express high IRF4, which is essential for plasma cell generation. We found the CpG sites in Irf4 locus that are demethylated specifically in plasma cells in Tet2/3-dependent manner. These results suggest that DNA demethylation in these sites are required for high IRF4 expression and subsequent plasma cell generation.

Academic Significance and Societal Importance of the Research Achievements

抗体分子は生体に侵入してくるウイルスなどの外来異物を排除するのに必要不可欠な分子である。中でも高親和性の抗体はウイルスなどの中和活性が高く、高親和性抗体をいかに誘導するかがワクチンの成否を握ると考えられている。しかし高親和性抗体を生み出す仕組みは理解されていなかった。本研究では、高親和性抗体が生み出される場である胚中心におけるB細胞・プラズマ細胞の選択機構を明らかにすることができた。またエピジェネティック変化がプラズマ細胞分化を制御する機構も明らかにできた。本研究で得られた成果は効率の良いワクチン開発に重要な知見を与えるものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2020 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Invited: 2 results)

  • [Journal Article] Plasma Cell Differentiation2020

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

      Adv. Exp. Med. Biol.

      Volume: 1254 Pages: 63-74

    • DOI

      10.1007/978-981-15-3532-1_6

    • ISBN
      9789811535314, 9789811535321
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma cell differentiation during the germinal center reaction2019

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

      Immunological Reviews

      Volume: 288 Issue: 1 Pages: 64-74

    • DOI

      10.1111/imr.12751

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate2018

    • Author(s)
      Ise Wataru、Fujii Kentaro、Shiroguchi Katsuyuki、Ito Ayako、Kometani Kohei、Takeda Kiyoshi、Kawakami Eiryo、Yamashita Kazuo、Suzuki Kazuhiro、Okada Takaharu、Kurosaki Tomohiro
    • Journal Title

      Immunity

      Volume: 48 Issue: 4 Pages: 702-715

    • DOI

      10.1016/j.immuni.2018.03.027

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help.2017

    • Author(s)
      Inoue T, Shinnakasu R, Ise W, Kawai C, Egawa T, Kurosaki T.
    • Journal Title

      J. Exp. Med.

      Volume: 214 Issue: 4 Pages: 1181-1198

    • DOI

      10.1084/jem.20161263

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Regulation of plasma cell differentiation from germinal center2019

    • Author(s)
      Wataru Ise
    • Organizer
      日本免疫学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] The heightened T-B interaction associates with plasma-prone germinal center B cells2017

    • Author(s)
      伊勢 渉
    • Organizer
      免疫学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 液性記憶免疫応答を担うB細胞の分化とその選択機構2017

    • Author(s)
      伊勢 渉
    • Organizer
      日本食品免疫学会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-04-28   Modified: 2021-02-19  

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