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A role of ADAR1 in induction of somatic hypermutation

Research Project

Project/Area Number 23659239
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionChiba University

Principal Investigator

TOKUHISA Takeshi  千葉大学, 大学院・医学研究院, 教授 (20134364)

Co-Investigator(Kenkyū-buntansha) ARIMA Masafumi  千葉大学, 大学院・医学研究院, 講師 (00202763)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords獲得免疫 / 体細胞超突然変異 / Bリンパ球 / 胚中心 / サイトカイン / クラススイッチ
Research Abstract

We examined a role of Adenosine deaminase acting on RNA1(ADAR1) in induction of somatic hypermutation (SHM) in germinal center (GC) B cells using ADAR1-transgenic (ADAR1-Tg) and ADAR1-conditional deficient (ADAR1-cKO) mice. After ADAR1-Tg and ADAR1-cKO mice were immunized with NP-CG on Alum, the frequency of SHM in the VH186.2 gene of GC B cells were analyzed. The frequencies in ADAR1-Tg GC B cells and in ADAR1-cKO GC B cells were higher and lower than that in wild type GC B cells, respectively. Thus, ADAR1 plays a role in induction of somatic hypermutations in GC B cells.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (33 results)

All 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (11 results) (of which Invited: 1 results) Book (3 results) Remarks (3 results)

  • [Journal Article] ADAR1 protein induces adenosine-targeted DNA mutations in senescent Bcl6 gene-deficient cells2013

    • Author(s)
      Tsuruoka, N., Arima, M., Yoshida, N., Okada, S., Sakamoto, A., Hatano, M., Satake, H., Arguni, E., Wang, Ji-Y., Yang,J-H., Nishikura, K., Sekiya, S., Shozu, M., and Tokuhisa, T.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Pages: 826-836

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Generation of tissue- specific H-2K(d) transgenic mice for the study of K(d)-restricted malariaepitope-specific CD8(+) T-cell responses in vivo2013

    • Author(s)
      Huang, J., Li, X., Kohno, K., Hatano, M., Tokuhisa, T., Murray, P.J., Brocker, T., and Tsuji, M.
    • Journal Title

      J. Immunol. Methods

      Volume: 387 Pages: 254-261

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] ADAR1 protein induces adenosine-targeted DNA mutations in senescent Bcl6 gene-deficient cells.2013

    • Author(s)
      Tsuruoka, N.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Pages: 826-836

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of the IgM Fc receptor in IgM homeostasis, B cell survival, and humoral immune responses2012

    • Author(s)
      Ouchida, R., Mori, H., Hase, K., Takatsu, H., Kurosaki, T., Tokuhisa, T., Ohno, H., and Wang, Ji-Yang
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 109 Pages: 2699-2706

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema2012

    • Author(s)
      Shigeta, A., Tada, Y., Wang, J.Y., Ishizaki, S., Tsuyusaki, J., Yamauchi, K., Kasahara, Y., Iesato, K., Tanabe, N., Takiguchi, Y., Sakamoto, A., Tokuhisa, T., Shibuya, K., Hiroshima, K., West, J., and Tatsumi, K.
    • Journal Title

      Am. J. Physiol. Lung Cell Mol. Physiol.

      Volume: 303 Pages: 141-151

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] BAZF, a novel component ofcullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signalling in angiogenesis.2012

    • Author(s)
      Ohnuki, H., Inoue, H., Takemori, N., Nakayama, H., Sakaue, T., Fukuda, S., Miwa, D., Nishiwaki, E., Hatano, M., Tokuhisa, T., Endo, Y., Nose, M., and Higashiyama, S.
    • Journal Title

      Blood

      Volume: 119 Pages: 2688-2698

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of the IgM Fc receptor in IgM homeostasis, B cell survival, and humoral immune responses.2012

    • Author(s)
      Ouchida, R.
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 109 Pages: 2699-2706

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signalling in angiogenesis.2012

    • Author(s)
      Ohnuki, H.
    • Journal Title

      Blood

      Volume: 119 Pages: 2688-2698

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bcl6 in pulmonary epithelium coordinately controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation2011

    • Author(s)
      Seto, T., Yoshitake, M., Ogasawara, T., Ikari, J, Sakamoto, A., Hatano, M., Hirata, H., Fukuda, T., Kuriyama, T., Tatsumi, K., Tokuhisa, T., and Arima, M.
    • Journal Title

      Clin. Exp. Allergy

      Volume: 41 Pages: 1568-1578

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Over-expression of the LTC(4) synthase gene in mice reproduces human aspirin-induced asthma2011

    • Author(s)
      Hirata, H., Arima, M., Fukushima, Y., Honda, K., Sugiyama, K., Tokuhisa, T., and Fukuda, T.
    • Journal Title

      Clin. Exp. Allergy

      Volume: 41 Pages: 1133-1142

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Outcome prediction in sepsis combined use of genetic polymorphisms -A study in Japanese population2011

    • Author(s)
      Shimada, T., Oda, S., Sadahiro, T., Nakamura, M., Hirayama, Y., Watanabe, E., Abe, R., Nakada, T.A., Tateishi, Y.,Otani, S., Hirasawa, H., Tokuhisa, T., and Uno, H.
    • Journal Title

      Cytokine

      Volume: 54 Pages: 79-84

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] CXCR4 expression on activated B cells is down-regulated by CD63 and IL-212011

    • Author(s)
      Yoshida, N., Kitayama, D., Arima, M., Sakamoto, A., Inamine, A., Takano, H., Hatano, M., Koike, T., and Tokuhisa, T
    • Journal Title

      J. Immunol.

      Volume: 186 Pages: 2800-2808

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bcl6 is required for the development of mouse CD4^+and DC・^+ dendritic cells.2011

    • Author(s)
      Ohtsuka, H., Sakamoto, A., Pan, J., Inage, S., Horigome, S., Ichii, H., Arima, M., Hatano, M., Okada, S., and Tokuhisa, T.
    • Journal Title

      J. Immunol.

      Volume: 186 Pages: 255-263

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bcl6 is required for the development---2011

    • Author(s)
      Ohtsuka, et al.
    • Journal Title

      J. Immunol.

      Volume: 186 Pages: 255-263

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] CXCR4 expression on activated B cells---2011

    • Author(s)
      Yoshida, et al.
    • Journal Title

      J. Immunol.

      Volume: 186 Pages: 2800-2808

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bcl6 in pulmonary epithelium---2011

    • Author(s)
      Seto, et al.
    • Journal Title

      Clin. Exp. Allergy

      Volume: 41 Pages: 1568-1578

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] アレルギーは治せるか2012

    • Author(s)
      徳久剛史
    • Organizer
      松戸東病院セミナー
    • Place of Presentation
      松戸市
    • Year and Date
      2012-11-16
    • Related Report
      2012 Final Research Report
  • [Presentation] 将来構想に基づく博士課程教育リーディングプログラム2012

    • Author(s)
      徳久剛史
    • Organizer
      神戸大G-COEセミナー
    • Place of Presentation
      神戸市
    • Year and Date
      2012-10-17
    • Related Report
      2012 Final Research Report
  • [Presentation] 免疫記憶細胞の形成と維持2012

    • Author(s)
      徳久剛史
    • Organizer
      第40回日本臨床免疫学会教育講演
    • Place of Presentation
      東京
    • Year and Date
      2012-09-29
    • Related Report
      2012 Final Research Report
  • [Presentation] 若き臨床研究者たちへ2012

    • Author(s)
      徳久剛史
    • Organizer
      第51回日本鼻科学会特別講演
    • Place of Presentation
      千葉市
    • Year and Date
      2012-09-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 免疫記憶と慢性アレルギー2012

    • Author(s)
      徳久剛史
    • Organizer
      第6回日本アミノ酸学会特別講演
    • Place of Presentation
      松戸市
    • Year and Date
      2012-09-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 免疫記憶細胞の形成と維持2012

    • Author(s)
      徳久剛史
    • Organizer
      市川免疫研究会
    • Place of Presentation
      市川市
    • Year and Date
      2012-06-27
    • Related Report
      2012 Final Research Report
  • [Presentation] B cell activation and memory2011

    • Author(s)
      Tokuhisa T.
    • Organizer
      第40回日本免疫学会 シンポジウ ム
    • Place of Presentation
      千葉市
    • Year and Date
      2011-11-27
    • Related Report
      2012 Final Research Report
  • [Presentation] B cell activation and memory2011

    • Author(s)
      Tokuhisa T.
    • Organizer
      第40回日本免疫学会シンポジウ ム
    • Place of Presentation
      千葉市
    • Year and Date
      2011-11-27
    • Related Report
      2012 Final Research Report
  • [Presentation] 老化すると免疫記憶にもボケがでるか?2011

    • Author(s)
      徳 久剛史
    • Organizer
      第11回日本抗加齢医学会シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2011-05-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 免疫記憶細胞の形成と維持

    • Author(s)
      徳久剛史
    • Organizer
      日本臨床免疫学会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] B cell activation and memory

    • Author(s)
      Tokuhisa, T.
    • Organizer
      日本免疫学会(招待講演)
    • Place of Presentation
      千葉市
    • Related Report
      2011 Research-status Report
  • [Book] B細胞免疫記憶研究の最先端と今後の展望2012

    • Author(s)
      徳久剛史
    • Publisher
      羊土社、実験医学
    • Related Report
      2012 Final Research Report
  • [Book] 耐性と免疫記憶2012

    • Author(s)
      徳久剛史
    • Publisher
      東京医学社、小児内科
    • Related Report
      2012 Final Research Report
  • [Book] 胚中心におけるB細胞の移動とCXCR4の発現調節2012

    • Author(s)
      吉田修也,徳久剛史
    • Publisher
      科学評論社、臨床免疫・アレルギー科
    • Related Report
      2012 Final Research Report
  • [Remarks] 分化制御学教室のホームページのURLは、以下の通りである。

    • URL

      http://www.m.chiba-u.ac.jp/class/devgen

    • Related Report
      2012 Final Research Report
  • [Remarks] 分化制御学

    • URL

      http://www.m.chiba-u.ac.jp/class/devgen/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.m.chiba-u.ac.jp/class/devgen/

    • Related Report
      2011 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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