A role of ADAR1 in induction of somatic hypermutation

• Project/Area Number: 23659239
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Chiba 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: ¥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.

Research Products

• [Journal Article] ADAR1 protein induces adenosine-targeted DNA mutations in senescent Bcl6 gene-deficient cells (2013)
  • 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
  • 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 vivo (2013)
  • 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
  • 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
  • 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., 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
  • Peer Reviewed
• [Journal Article] CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema (2012)
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Bcl6 in pulmonary epithelium coordinately controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Over-expression of the LTC(4) synthase gene in mice reproduces human aspirin-induced asthma (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Outcome prediction in sepsis combined use of genetic polymorphisms -A study in Japanese population (2011)
  • 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
  • Peer Reviewed
• [Journal Article] CXCR4 expression on activated B cells is down-regulated by CD63 and IL-21 (2011)
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Bcl6 in pulmonary epithelium--- (2011)
  • Author(s): Seto, et al.
  • Journal Title: Clin. Exp. Allergy Volume: 41 Pages: 1568-1578
  • 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
• [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
• [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
• [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
• [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
• [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
• [Presentation] B cell activation and memory (2011)
  • 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
• [Presentation] B cell activation and memory (2011)
  • 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
• [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
• [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）
  • 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
• [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
• [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
• [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
• [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
• [Remarks] 分化制御学
  • URL: http://www.m.chiba-u.ac.jp/class/devgen/
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/devgen/