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Molecular bases enabling various BCR responses

Research Project

Project/Area Number 22K19424
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 InstitutionThe University of Tokyo

Principal Investigator

Miyake Kensuke  東京大学, 医科学研究所, 教授 (60229812)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsToll様受容体 / B細胞受容体
Outline of Research at the Start

B細胞抗原受容体(B cell receptor、BCR)は、増殖、活性化、死滅まで多様な応答を誘導するが、その分子基盤は不明である。一部のB細胞リンホーマにおいてはBCR-TLR9複合体が増殖を誘導する。このBCR-TLR複合体が正常なB細胞の増殖にも関与するのか検討する。BCRとTLR9あるいはBCRとTLR7について、増殖を誘導するために必要な複合体構成分子の同定を進める。さらにBCR-TLR複合体とBCR単独とを比較し、複合体が異なる応答を誘導している可能性を検討する。これらの解析を通して、BCR-TLR複合体が多様なBCR応答説明する分子基盤のひとつであることを示す。

Outline of Final Research Achievements

The antigen receptor expressed on B cells (B cell receptor, BCR) induces a variety of responses, from proliferation to activation and cell death. Little is known about the molecular basis of this diversity. We hypothesized that the diversity depends on various forms of BCRs such as BCR alone and the BCR-TLR complex, and that the latter induces survival and proliferation. We expressed BCR and TLR9 in the IL-3-dependent cell line Ba/F3. Using these cells, we investigated whether survival and proliferation could be induced in the absence of IL-3. As a result, survival and proliferation were induced in the presence of both anti-IgM antibody and the TLR9 ligand. This cell line is valuable to study the molecular basis of BCR-induced survival and proliferation.

Academic Significance and Societal Importance of the Research Achievements

B細胞受容体からのシグナルは活性化、増殖、分化など多様なB細胞応答を誘導するがその分子基盤は不明である。応答の多様性を説明する分子基盤として、BCRとTLR9との複合体を解析するための細胞株を確立することに成功した。この細胞を用いることで、BCR-TLR9複合体の形成や活性化に関わる分子の検索などが可能となる。その解析で得られる知見はB細胞の生存・増殖の制御に重要であることが予想される。つまり、抗体産生を誘導するアジュバントの開発やB細胞リンホーマの治療薬開発に資することが期待できる。

Report

(2 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (12 results)

All 2024 2023

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results)

  • [Journal Article] A stress sensor, IRE1α, is required for bacterial-exotoxin-induced interleukin-1β production in tissue-resident macrophages2024

    • Author(s)
      I. Sasaki, Y. Fukuda-Ohta, C. Nakai, N. Wakaki-Nishiyama, C. Okamoto, D. Okuzaki, S. Morita, S. Kaji, Y. Furuta, H. Hemmi, T. Kato, A. Yamamoto, E. Tosuji, SI Saitoh, T. Tanaka, K. Hoshino, S. Fukuda, K. Miyake, E. Kuroda, KJ Ishii, T. Iwawaki, K. Furukawa, T. Kaisho.
    • Journal Title

      Cell Reports

      Volume: 43 Issue: 4 Pages: 113981-113981

    • DOI

      10.1016/j.celrep.2024.113981

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant monocytopoiesis drives granuloma development in sarcoidosis2023

    • Author(s)
      Hiranuma Ryosuke、Sato Ryota、Yamaguchi Kiyoshi、Nakamizo Satoshi、Asano Kenichi、Shibata Takuma、Fukui Ryutaro、Furukawa Yoichi、Kabashima Kenji、Miyake Kensuke
    • Journal Title

      International Immunology

      Volume: 36 Issue: 4 Pages: 183-196

    • DOI

      10.1093/intimm/dxad054

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular aaRSs drive autoimmune and inflammatory responses in rheumatoid arthritis via the release of cytokines and PAD42023

    • Author(s)
      Kimura A, Takagi T, Thamamongood T, Sakamoto S, Ito T, Seki I, Okamoto M, Aono H, Serada S, Naka T, Imataka H, Miyake K, Ueda T, Miyanokoshi M, Wakasugi K, Iwamoto N, Ohmagari N, Iguchi T, Nitta T, Takayanagi H, Yamashita H, Kaneko H, Tsuchiya H, Fujio K, Handa H, Suzuki H.
    • Journal Title

      Annals of the Rheumatic Diseases

      Volume: 82 Issue: 9 Pages: 1153-1161

    • DOI

      10.1136/ard-2023-224055

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes.2023

    • Author(s)
      Kuchitsu Y, Mukai K, Uematsu R, Takaada Y, Shinojima A, Shindo R, Shoji T, Hamano S, Ogawa E, Sato R, Miyake K, Kato A, Kawaguchi Y, Nishitani-Isa M, Izawa K, Nishikomori R, Yasumi T, Suzuki T, Dohmae N, Uemura T, Barber GN, Arai H, Waguri S, Taguchi T.
    • Journal Title

      Nature Cell Biology

      Volume: 25 Issue: 3 Pages: 453-466

    • DOI

      10.1038/s41556-023-01098-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase2023

    • Author(s)
      Liu Gang、et al
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 7349-7349

    • DOI

      10.1038/s41467-023-42913-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TLR3 forms a laterally aligned multimeric complex along double-stranded RNA for efficient signal transduction2023

    • Author(s)
      Sakaniwa Kentaro、Fujimura Akiko、Shibata Takuma、Shigematsu Hideki、Ekimoto Toru、Yamamoto Masaki、Ikeguchi Mitsunori、Miyake Kensuke、Ohto Umeharu、Shimizu Toshiyuki
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 164-164

    • DOI

      10.1038/s41467-023-35844-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TLR7/8 stress response drives histiocytosis in SLC29A3 disorders2023

    • Author(s)
      Shibata Takuma、Sato Ryota、Taoka Masato、Saitoh Shin-Ichiroh、Komine Mayumi、(他16人)、Ohto Umeharu、Shimizu Toshiyuki、Ozawa Manabu、Yoshida Nobuaki、Isobe Toshiaki、Latz Eicke、Mukai Kojiro、Taguchi Tomohiko、Hemmi Hiroaki、Akira Shizuo、Miyake Kensuke
    • Journal Title

      Journal of Experimental Medicine

      Volume: 220 Issue: 9 Pages: 320230054-320230054

    • DOI

      10.1084/jem.20230054

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural basis for thioredoxin-mediated suppression of NLRP1 inflammasome2023

    • Author(s)
      Zhang Zhikuan、Shibata Takuma、Fujimura Akiko、Kitaura Jiro、Miyake Kensuke、Ohto Umeharu、Shimizu Toshiyuki
    • Journal Title

      Nature

      Volume: 622 Issue: 7981 Pages: 188-194

    • DOI

      10.1038/s41586-023-06532-4

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Presentation] Immune disorders due to lysosomal nucleic acid stress2023

    • Author(s)
      三宅 健介
    • Organizer
      The 2nd International Symposium of Clinical Immunology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Lysosomal nucleic acid stress diseases2023

    • Author(s)
      三宅 健介
    • Organizer
      JSICR/MMCB 2023 Joint Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] リソソーム核酸ストレスと疾患2023

    • Author(s)
      三宅 健介
    • Organizer
      日本外科代謝栄養学会第60回学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] リソソーム核酸ストレスと疾患2023

    • Author(s)
      三宅 健介
    • Organizer
      第42回日本認知症学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited

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Published: 2022-07-05   Modified: 2025-01-30  

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