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Development of in vitro culture for peripheral B cell differentiation into plasma cell

Research Project

Project/Area Number 24659587
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionNagoya University

Principal Investigator

KOBAYASHI Takaaki  名古屋大学, 医学(系)研究科(研究院), 寄附講座教授 (70314010)

Co-Investigator(Kenkyū-buntansha) HANEDA Masataka  名古屋大学, 大学院医学系研究科, 寄附講座講師 (50436995)
IWASAKI Kenta  名古屋大学, 大学院医学系研究科, 寄附講座講師 (10508881)
MIWA Yuko  名古屋大学, 大学院医学系研究科, 研究員 (90572941)
KUZUYA Takafumi  名古屋大学, 医学部附属病院, 薬剤部副長 (00444406)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords移植・再生医療 / Bリンパ球 / 形質細胞 / 培養 / HLA抗体 / 抗体
Research Abstract

We attempted to develop a novel in vitro culture assay for proliferation and differentiation of peripheral B cells into plasma cells. Using 3 step culture method, the difference in action points (in the process of B cell differentiation) between clinical available immunosuppressive agents such as calcineurin inhibitor (CNI), mTOR-inhibitor (mTOR-I), anti-metabolite and steroid was clarified. The results showed anti-metabolite, mTOR-I and steroid could suppress B cells in the early, middle and late phase, respectively. Effective method for HLA antibody secretion in the B cell culture system has been established using APRIL (A proliferation-inducing ligand), BAFF (B cell activating factor), mitogen-stimulated T cell secretion and adipose-derived mesenchymal stem cells. We can move on to the next step to evaluate early diagnosis of chronic antibody mediated rejection.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (37 results)

All 2014 2013 2012

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (26 results)

  • [Journal Article] Comparative analysis of drug action on B-cell proliferation and differentiation for mycophenolic acid, everolimus, and prednisolone.2014

    • Author(s)
      Haneda M, Owaki M, Kuzuya T, Iwasaki K, Miwa Y, Kobayashi T.
    • Journal Title

      Transplantation.

      Volume: 97 Issue: 11 Pages: 405-412

    • DOI

      10.1097/01.tp.0000441826.70687.f6

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation2014

    • Author(s)
      Satoshi Ashimine,Yoshihiko Watarai,Takayuki Yamamoto,Takahisa Hiramitsu,Makoto Tsujita,Koji Nanmoku,Norihiko Goto,Asami Takeda,Akio Katayama,Kazuharu Uchida and Takaaki Kobayashi
    • Journal Title

      Kidney International

      Volume: 85巻 Pages: 425-430

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Influence of olive-derived hydroxytyrosol on the toll-like receptor 4-dependent inflammatory response of mouse peritoneal macrophages2014

    • Author(s)
      Takeda Y,Bui VN,Iwasaki K,Kobayashi T,Ogawa H,Imai K
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 446巻 Issue: 4 Pages: 1225-1230

    • DOI

      10.1016/j.bbrc.2014.03.094

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation2014

    • Author(s)
      Satoshi Ashimine, Yoshihiko Watarai, Takayuki Yamamoto, Takahisa Hiramitsu, Makoto Tsujita, Koji Nanmoku, Norihiko Goto, Asami Takeda, Akio Katayama, Kazuharu Uchida and Takaaki Kobayashi
    • Journal Title

      Kidney International

      Volume: 85 Issue: 2 Pages: 425-430

    • DOI

      10.1038/ki.2013.291

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent development of subclinical chronic antibody-mediated rejection within 1 year after renal transplantation with pre-transplant positive donor-specific antibodies and negative CDC crossmatches2013

    • Author(s)
      Shigeyoshi Yamanaga,Yoshihiko Watarai,Takayuki Yamamoto,Makoto Tsujita,Takahisa Hiramitsu,Koji Nanmoku,Norihiko Goto,Asami Takeda,Kunio Morozumi,Akio Katayama,Hiroh Saji,Kazuharu Uchida,and Takaaki Kobayashi
    • Journal Title

      Human Immunology

      Volume: 74巻 Issue: 9 Pages: 1111-1118

    • DOI

      10.1016/j.humimm.2013.06.022

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] AMP-activated protein kinase as a promoting factor, but complement and thrombin as limiting factors for acquisition of cytoprotection: implications for induction of accommodation.2013

    • Author(s)
      Iwasaki K, Miwa Y, Haneda M, Kuzuya T, Ogawa H, Onishi A, Kobayashi T.
    • Journal Title

      Transpl Int.

      Volume: 26 Issue: 11 Pages: 1138-1148

    • DOI

      10.1111/tri.12186

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of 4E-BP1 predicts sensitivity to everolimus in gastric cancer cells2013

    • Author(s)
      Nishi T,Iwasaki K,Ohashi N,Tanaka C,Kobayashi D,Nakayama G,Koike M,Fujiwara M,Kobayashi T,Kodera Y
    • Journal Title

      Cancer Letters

      Volume: 331巻 Issue: 2 Pages: 220-229

    • DOI

      10.1016/j.canlet.2013.01.004

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of AMP-activated Protein Kinase in Ferritin H Gene Expression by Resveratrol in Human T cells2013

    • Author(s)
      Iwasaki Kenta,Ray Paul,Huang Bo-Wen,Sakamoto Kensuke,Kobayashi Takaaki,Tsuji Yoshiaki
    • Journal Title

      Biochemistry

      Volume: 52巻 Issue: 30 Pages: 2075-5083

    • DOI

      10.1021/bi400399f

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparative study on signal transduction in endothelial cells after anti-A/B and HLA antibody reaction : implication of accommodation2012

    • Author(s)
      Iwasaki K, Miwa Y, Ogawa H, Iwamoto M, Furusawa T, Onishi A, Kuzuya T, Haneda M, Watarai Y, Uchida K, Kobayashi T.
    • Journal Title

      Transplantation

      Volume: 93 Issue: 4 Pages: 390-397

    • DOI

      10.1097/tp.0b013e3182424df3

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Significance of C4d deposition in antibody-mediated rejection2012

    • Author(s)
      Takeda A,Otsuka Y,Horike K,Inaguma D,Hiramitsu T,Yamamoto T,Nanmoku K,Goto N,Watarai Y,Uchida K,Morozumi K,Kobayashi T
    • Journal Title

      Clin Transplantation

      Volume: 26 (Supple 24)巻 Pages: 43-48

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Significance of C4d deposition in antibody-mediated rejection2012

    • Author(s)
      Asami Takeda, Takaaki Kobayashi et al.
    • Journal Title

      Clinical Transplantation

      Volume: 26 (Suppl 24) Issue: s24 Pages: 43-48

    • DOI

      10.1111/j.1399-0012.2012.01642.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 抗体スクリーニングに基づく個別化免疫抑制法2013

    • Author(s)
      小林孝彰
    • Organizer
      29回腎移植血管外科研究会
    • Place of Presentation
      青森県浅虫温泉海扇閣、青森
    • Year and Date
      2013-06-29
    • Related Report
      2013 Final Research Report
  • [Presentation] Peripheral B cell culture for assessment of immune response to ABO blood type carbohydrate antigens2013

    • Author(s)
      Masataka Haneda,Yoshiko Matsuda,Yuko Miwa,Kenta Iwasaki,Yoshihiko Watarai,Kazuharu Uchida,Takaaki Kobayashi
    • Organizer
      International Xenotransplantation Association (IXA) 2013
    • Place of Presentation
      Osaka International Congress Center,Osaka (Japan)
    • Related Report
      2013 Final Research Report
  • [Presentation] The impact of TNF-alpha cytokine family on the B cell assay in vitro - naive B cell differentiation for long lived plasma cell2013

    • Author(s)
      Yoshiko Matsuda,Masataka Haneda,Takahisa Hiramitsu,Yoshihiko Watarai,Takaaki Kobayashi
    • Organizer
      3rd ESOT Basic Science Meeting/13th TTS Basic Science Meeting
    • Place of Presentation
      Paris (France)
    • Related Report
      2013 Final Research Report
  • [Presentation] In vitroにおけるTumor necrosis family-alpha(TNF-α) cytokineのB細胞培養系への影響2013

    • Author(s)
      松田佳子、稲永由紀子、平光高久、三輪祐子、岩崎研太、羽根田正隆、小林孝彰
    • Organizer
      49回日本移植学会
    • Place of Presentation
      国立京都国際会館、京都
    • Related Report
      2013 Final Research Report
  • [Presentation] リコンビナント抗血液型A型糖鎖糖鎖IgG抗体の作成2013

    • Author(s)
      羽根田正隆、三輪祐子、岩崎研太、小林孝彰
    • Organizer
      49回日本移植学会
    • Place of Presentation
      国立京都国際会館、京都
    • Related Report
      2013 Final Research Report
  • [Presentation] In vitro形質細胞分化誘導系を用いた、血液型糖鎖抗原に対する抗体産生系の確立2013

    • Author(s)
      羽根田正隆、成田由紀子、三輪祐子、岩崎研太、小林孝彰
    • Organizer
      49回日本移植学会
    • Place of Presentation
      国立京都国際会館、京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Plasma cell maturation and transformation in vitro2013

    • Author(s)
      Yoshiko Matsuda,Yuko Miwa,Kenta Iwasaki,Masataka Haneda,Takaaki Kobayashi
    • Organizer
      Congress of Asian Society of Transplantation (CAST) 2013
    • Place of Presentation
      Kyoto International Conference Center,Kyoto (Japan)
    • Related Report
      2013 Final Research Report
  • [Presentation] The impact of the tumor necrosis factor-alpha family on B cell proliferation in vitro2013

    • Author(s)
      Yoshiko Matsuda,Yuko Miwa,Kenta Iwasaki,Masataka Haneda,Takaaki Kobayashi
    • Organizer
      Congress of Asian Society of Transplantation (CAST) 2013
    • Place of Presentation
      Kyoto International Conference Center,Kyoto (Japan)
    • Related Report
      2013 Final Research Report
  • [Presentation] In Vitro Differentiation of Naive/Memory B Cells into Plasma Cells : Difference in Mode of Drug Action between Mycophenolic Acid and Everolimus2013

    • Author(s)
      M. Haneda,M. Owaki,K. Iwasaki,Y. Miwa,Y. Watarai,K. Uchida,T. Kobayashi
    • Organizer
      American Transplant Congress 2013
    • Place of Presentation
      Seattle (USA)
    • Related Report
      2013 Final Research Report
  • [Presentation] Plasma cell maturation and transformation in vitro2013

    • Author(s)
      Yoshiko Matsuda, Yuko Miwa, Kenta Iwasaki, Masataka Haneda, Takaaki Kobayashi
    • Organizer
      Congress of Asian Society of Transplantation (CAST) 2013
    • Place of Presentation
      Kyoto International Conference Center (Kyoto, Japan)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The impact of the tumor necrosis factor-alpha family on B cell proliferation in vitro2013

    • Author(s)
      Yoshiko Matsuda, Yuko Miwa, Kenta Iwasaki, Masataka Haneda, Takaaki Kobayashi
    • Organizer
      Congress of Asian Society of Transplantation (CAST) 2013
    • Place of Presentation
      Kyoto International Conference Center (Kyoto, Japan)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Peripheral B cell culture for assessment of immune response to ABO blood type carbohydrate antigens2013

    • Author(s)
      Masataka Haneda, Yoshiko Matsuda, Yuko Miwa, Kenta Iwasaki, Yoshihiko Watarai, Kazuharu Uchida, Takaaki Kobayashi
    • Organizer
      Congress of Asian Society of Transplantation (CAST) 2013
    • Place of Presentation
      Kyoto International Conference Center (Kyoto, Japan)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The impact of TNF-alpha cytokine family on the B cell assay in vitro - naive B cell differentiation for long lived plasma cell2013

    • Author(s)
      Yoshiko Matsuda, Masataka Haneda , Takahisa Hiramitsu, Yoshihiko Watarai, Takaaki Kobayashi
    • Organizer
      3rd ESOT Basic Science Meeting/13th TTS Basic Science Meeting
    • Place of Presentation
      Paris, France
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vitroにおけるTumor necrosis family-alpha(TNF-α) cytokineのB細胞培養系への影響2013

    • Author(s)
      松田佳子、稲永由紀子、平光高久、三輪祐子、岩﨑研太、羽根田正隆、小林孝彰
    • Organizer
      49回日本移植学会総会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] リコンビナント抗血液型A型糖鎖糖鎖IgG抗体の作成2013

    • Author(s)
      羽根田正隆、三輪祐子、岩﨑研太、小林孝彰
    • Organizer
      49回日本移植学会総会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vitro 形質細胞分化誘導系を用いた、血液型糖鎖抗原に対する抗体産生系の確立2013

    • Author(s)
      羽根田正隆、成田由紀子、三輪祐子、岩﨑研太、小林孝彰
    • Organizer
      49回日本移植学会総会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] In Vitro Differentiation of Naive/Memory B Cells into Plasma Cells: Difference in Mode of Drug Action between Mycophenolic Acid and Everolimus2013

    • Author(s)
      Masataka Haneda, Takaaki Kobayashi et al.
    • Organizer
      American Transplant Congress 2013
    • Place of Presentation
      Washington State Convention & Trade Center (Seattle: USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] Expansion of donor sources.Hurdles of xenotransplantation2012

    • Author(s)
      Takaaki Kobayashi
    • Organizer
      The 42nd Annual Congress of the Korean Society for Transplantation & The 9th Korea-Japan Transplantation Forum
    • Place of Presentation
      Incheon (Korea)
    • Related Report
      2013 Final Research Report
  • [Presentation] In vitro B cell differentiation assayを用いたDSA検出法の検討2012

    • Author(s)
      羽根田正隆、黒木聖久、成田由紀子、大脇麻未、葛谷孝文、岩崎研太、渡井至彦、打田和治、小林孝彰
    • Organizer
      48回日本移植学会
    • Place of Presentation
      愛知県産業労働センター、名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 免疫抑制薬の抗体産生抑制効果に対する薬力学解析の試み2012

    • Author(s)
      大脇麻未、成田由紀子、羽根田正隆、倉田洋子、葛谷孝文、網岡克雄、三輪祐子、岩崎研太、小林孝彰
    • Organizer
      48回日本移植学会
    • Place of Presentation
      愛知県産業労働センター、名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] No Inhibitory Effect of Pre-Transplant Desensitization Treatment with Rituximab or Splenectomy on de Novo HLA Antibody Production in Renal Transplantation2012

    • Author(s)
      Kobayashi T,Yamamoto T,Kuroki K,Hiramitsu T,Tsujita M,Goto N,Nanmoku K,Nagasaka T,Ohtsuka S,Katayama A,Watarai Y,Takeda A,Morozumi K,Uchida K
    • Organizer
      24th International Congress of The Transplantation Society
    • Place of Presentation
      Berlin (Germany)
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗体関連型拒絶反応(AMR)を予測しうる移植前検査法の開発2012

    • Author(s)
      三輪祐子、小林孝彰 他
    • Organizer
      ABO血液型不適合移植研究会
    • Place of Presentation
      ミッドランドスクエア ミッドランドホール(名古屋市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 移植前脱感作療法は長期のde novo HLA抗体産生を抑制するか?2012

    • Author(s)
      黒木聖久、小林孝彰 他
    • Organizer
      日本組織適合性学会
    • Place of Presentation
      明治大学(駿河台キャンパス)アカデミーコモン・リバティタワー(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] HLA,ABO抗原に対する抗体接着が引き起こす、免疫順応シグナル伝達2012

    • Author(s)
      岩﨑 研太、小林孝彰 他
    • Organizer
      日本組織適合性学会
    • Place of Presentation
      明治大学(駿河台キャンパス)アカデミーコモン・リバティタワー(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] In vitro B cell differentiation assay を用いたDSA検出法の検討2012

    • Author(s)
      羽根田正隆、小林孝彰 他
    • Organizer
      日本移植学会
    • Place of Presentation
      愛知県産業労働センター(ウインクあいち)(名古屋市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 免疫抑制薬の抗体産生抑制効果に対する薬力学解析の試み2012

    • Author(s)
      大脇麻未、小林孝彰 他
    • Organizer
      日本移植学会
    • Place of Presentation
      愛知県産業労働センター(ウインクあいち)(名古屋市)
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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