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Analysis of affinity maturation process of antibodies using a novel FDC line and its application.

Research Project

Project/Area Number 21360405
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biofunction/Bioprocess
Research InstitutionOkayama University

Principal Investigator

OMORI Hitoshi  岡山大学, 大学院・自然科学研究科, 教授 (70116440)

Co-Investigator(Renkei-kenkyūsha) MAGARI Masaki  岡山大学, 大学院・自然科学研究科, 助教
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2011: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2009: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywordsモノクローナル抗体 / リンパ球 / 突然変異 / アポトーシス / 生体防御 / 胚中心 / 抗体医薬 / 濾胞樹状細胞 / 抗体 / 体細胞高頻度突然変異 / 親和性成熟 / IL-21 / AID / B細胞株
Research Abstract

Using a novel murine follicular dendritic cell line, FL-Y, I analyzed affinity maturation process of antibodies focusing on B cell selection in germinal centers(GCs). I found that FL-Y cells induced B cell death in the presence of a helper T cell cytokine, IL-21. The B cell death was shown to be dependent on PGE2 produced from FL-Y cells, The IL-21/PGE2-induced B cell death implicates a new negative selection mechanism of B cells in GCs.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (33 results)

All 2012 2011 2010 2009 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (14 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] Activa-tion-induced cytidine deaminase(AID)-dependent somatic hypermutation requires a splice isoform of the serine/arginine-rich(SR) protein SRSF12012

    • Author(s)
      Kanehiro, Y., Ohmori, H. Kanayama, N., et al.(10名中9番目)
    • Journal Title

      Proceeding of the National Academy of Sciences, USA.

      Volume: 109 Pages: 1216-1271

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation-induced cytidine deaminase (AID)-dependent somatic hypermutation requires a splice isoform of the serine/arginine-rich (SR) protein SRSF12012

    • Author(s)
      Kanehiro, Y., Ohmori, H.Kanayama, N., at al
    • Journal Title

      Proceeding of the National Academy of Sciences, USA

      Volume: 109 Issue: 4 Pages: 1216-1271

    • DOI

      10.1073/pnas.1120368109

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-21-dependent B cell death driven by prostaglandin E2, a product secreted from follicular dendritic cells2011

    • Author(s)
      Magari, M. Ohmori, H., et al.(7名中7番目)
    • Journal Title

      Journal of Immunology

      Volume: 187 Pages: 4210-4218

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of mesen-chyme-specific gene signatures by follicular dendritic cells : insights from the meta-analysis of microarray data frommultiple mouse cell popu-lations2011

    • Author(s)
      Mabbott, N., Ohmori, H., et al.(8名中6番目)
    • Journal Title

      Immunology

      Volume: 133 Pages: 482-498

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of mesenchyme-specific gene signatures by follicular dendritic cells : insights from the meta-analysis of microarray data from multiple mouse cell populations2011

    • Author(s)
      Mabbott, N., Ohmori, H., et al
    • Journal Title

      Immunology

      Volume: 133 Issue: 4 Pages: 482-498

    • DOI

      10.1111/j.1365-2567.2011.03461.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-21-dependent B cell death driven by prostaglandin E2, a product secre ted from follicular dendritic cells2011

    • Author(s)
      Magari, M.Ohmori, H., et al
    • Journal Title

      Journal of Immunology

      Volume: 187 Issue: 8 Pages: 4210-4218

    • DOI

      10.4049/jimmunol.1100934

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhance-ment of hypermutation frequency in the chicken B cell line DT40 for Efficient diversification of antibody repertoire.2010

    • Author(s)
      Magari, M., Kanehiro, Y., Ohmori, H., et al.(6名中6番目)
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 396 Pages: 353-358

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficient affinity maturation of antibodies in an engineered chicken B cell line DT40-SW by increasing point mutation.2010

    • Author(s)
      Kajita, M., Kanayama, N. Ohmori, H., et al.(7名中7番目)
    • Journal Title

      J. Biosci. Bioeng.

      Volume: 351 Pages: 351-358

    • NAID

      110007730029

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of hypermutation frequency in the chicken B cell line DT40 for efficient diversification of antibody repertoire.2010

    • Author(s)
      Magari, M., Kanehiro, Y., Todo, K., Ikeda, M., Kanayama, N., Ohmori, H.
    • Journal Title

      Biochem.Biphys.Res.Commmun.

      Volume: 396 Pages: 353-358

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient affinity maturation of antibodies in an engineered chicken B cell line DT40-SW by increasing point mutation2010

    • Author(s)
      Kajita, M., Okazawa, T., Ikeda, M., Todo, K., Magari, M., Kanayama, N., Ohmori, H.
    • Journal Title

      J.Biosci.Bioeng.

      Volume: 351 Pages: 351-358

    • NAID

      110007730029

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conditional transformation of immunoglobulin mutation pattern from gene conversion to point mutation by controlling XRCC3 expression in the DT40 B cell line.2010

    • Author(s)
      Kajita, M., Hagari, M., Todo, K., Kanayama, N., Ohmori, H.
    • Journal Title

      Journal of Bioscience and Bioengoneering 109

      Pages: 407-410

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of antibody production from a chicken B cell line DT40 by reducing Pax5 expression.2009

    • Author(s)
      Magari, M., Aya, T., Ikeda, M., Todo, K.Kanayam, N., Ohmori, H.
    • Journal Title

      Journal of Bioscience and Bieengineering 107

      Pages: 206-209

    • NAID

      110007110260

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] DT40を用いるin vitro抗体作製・改良システムの開発2011

    • Author(s)
      金山直樹, 他2名
    • Organizer
      日本分子生物学会大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2011-12-13
    • Related Report
      2011 Final Research Report
  • [Presentation] DT40を用いるin vitro抗体作製・改良システムの開発2011

    • Author(s)
      金山直樹、曲正樹、大森齊
    • Organizer
      日本分子生物学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)(招待講演)
    • Year and Date
      2011-12-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] IL-34依存性の新規な単球系細胞の機能解析2011

    • Author(s)
      松井一恵, 他5名
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      幕張メッセ(千葉)
    • Year and Date
      2011-11-28
    • Related Report
      2011 Final Research Report
  • [Presentation] IL-34依存性の新規単球系細胞の機構解析2011

    • Author(s)
      松井一恵、大森齊, 他5名
    • Organizer
      日本免疫学会大会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2011-11-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 変異導入能力を有する培養B細胞株を用いたin vitro抗体作製システムの高機能化2010

    • Author(s)
      金山直樹, 他5名
    • Organizer
      日本分子生物学会、日本生化学会合同大会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2010-12-09
    • Related Report
      2011 Final Research Report
  • [Presentation] 変異導入能力を有する培養B細胞株を用いたin vitro抗体作製システムの高機能化2010

    • Author(s)
      金山直樹、曲正樹、梶田真道、金広優一、藤堂景史、大森齊
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] 変異能力を有するニワトリB細胞株を用いた抗体の親和性成熟 : DT40-SWを用いたマウスモノクローナル抗体の改変2009

    • Author(s)
      金山直樹、小島聡史、藤井忍、北村幸一、井上和恵、岡山展久、松田修一、藤堂景史、曲正樹、大森齊
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] 変異能力を有するニワトリB細胞株を用いた抗体の親和性成熟 : 外来の抗体可変部遺伝子のDT40-SWにおける発現・改良系の構築2009

    • Author(s)
      小島聡史、藤井忍、北村幸一、井上和恵、岡山展久、松田修一、藤堂景史、曲正樹、金山直樹、大森齊
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] FDCとIL-21の関与する胚中心B細胞の新規な負の選択機構2009

    • Author(s)
      藤井康正, 他4名
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2009-12-03
    • Related Report
      2011 Final Research Report
  • [Presentation] FDCとIL-21の関与する胚中心B細胞の新規な負の選択機構2009

    • Author(s)
      藤井康正、西川裕美子、西尾裕美、金山直樹、大森齊
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2009-12-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] DT40-SWを用いるin vitro抗体作製システムの高機能化 : 変異様式の転換による高性能抗体作製2009

    • Author(s)
      梶田真道、曲正樹、藤堂景史、金山直樹、大森齊
    • Organizer
      日本生物工学会大会
    • Place of Presentation
      名古屋大学(愛知県)
    • Year and Date
      2009-09-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] DT40-SWを用いるin vitro抗体作製システムの高機能化 : 遺伝子変換と点突然変異の転換システムの構築2009

    • Author(s)
      曲正樹、梶田真道、金山直樹、大森齊
    • Organizer
      日本生物工学会大会
    • Place of Presentation
      名古屋大学(愛知県)
    • Year and Date
      2009-09-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 抗体の親和性成熟機構の解析とそれに基づく効率的in vitro抗体作製システムの開発2009

    • Author(s)
      大森斉
    • Organizer
      蛋白質と酵素の構造と機能に関する九州シンポジウム
    • Place of Presentation
      唐津シーサイドホテル(佐賀)
    • Year and Date
      2009-09-11
    • Related Report
      2011 Final Research Report
  • [Presentation] 抗体の親和性成熟機構の解析とそれに基づく効率的in vitro抗体作製システムの開発2009

    • Author(s)
      大森齊
    • Organizer
      蛋白質と酵素の構造と機能に関する九州シンポジウム
    • Place of Presentation
      唐津シーサイドホテル(佐賀県)
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Book] 改訂細胞工学2010

    • Author(s)
      永井和夫、大森斉、金山直樹、町田千代子
    • Total Pages
      230
    • Publisher
      講談社
    • Related Report
      2011 Final Research Report
  • [Book] 改訂 細胞工学2010

    • Author(s)
      永井和男、大森齊、町田千代子、金山直樹
    • Total Pages
      230
    • Publisher
      講談社サイエンティフィック
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.eng.okayama-u.ac.jp/eng_biotech/html/

    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞の遺伝子変異機能の制御による変異タンパク質の作製方法2011

    • Inventor(s)
      金山直樹、大森斉
    • Industrial Property Rights Holder
      岡山大学
    • Acquisition Date
      2011-04-09
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] ヒト型抗体を産出するB細胞の作製方法2010

    • Inventor(s)
      金山直樹、大森斉
    • Industrial Property Rights Holder
      岡山大学
    • Filing Date
      2010-11-18
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] ヒト型抗体を産出するB細胞の作製方法2010

    • Inventor(s)
      金山直樹、大森齊
    • Industrial Property Rights Holder
      岡山大学
    • Industrial Property Number
      2010-258404
    • Filing Date
      2010-11-18
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞の遺伝子変異機能の制御による変異タンパク質の作製方法2010

    • Inventor(s)
      大森齊、金山直樹
    • Industrial Property Rights Holder
      岡山大学
    • Acquisition Date
      2010-04-09
    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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