Identification of novel essential factors responsible for class switch recombination of immunoglobulin genes.

• Project/Area Number: 20590490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: SHINKURA Reiko Kyoto University, バイオサイエンス学部, 教授 (50362471)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 抗体 / クラススイッチ / 体細胞突然変異 / AID / DNA組み換え / DNA組みかえ

Research Abstract

Activation-induced cytidine deaminase (AID) is essential for class switch recombination of immunoglobulin genes. AID is required to introduce DNA lesions into switch region of immunoglobulin genes. However, an important question remains concerning how AID leads to double-strand DNA cleavage in switch region. Based on the hypothesis that a protein coded by the mRNA edited by AID generates DNA cleavage, I performed a rescue experiment for class switch recombination in AID-deficient B cells using retroviral cDNA library. Several candidate genes are now analyzed to confirm its role in class switch recombination.

Research Products

• [Journal Article] Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. (2011)
  • Author(s): Wei M, Shinkura R, Doi Y, Maruya M, Fagarasan S, Honjo T.
  • Journal Title: Nature Immunology 12 Pages: 264-270
  • Peer Reviewed
• [Journal Article] Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. (2011)
  • Author(s): Wei M, Shinkura R, Doi Y, Maruya M, Fagarasan S, Honjo T.
  • Journal Title: Nature Immunology Volume: 12 Pages: 264-270
  • Peer Reviewed
• [Journal Article] AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model. (2010)
  • Author(s): Komeno Y, Kitaura J, Watanabe-Okochi N, Kato N, Oki T, Nakahara F, Harada Y, Harada H, Shinkura R, Nagaoka H, Hayashi Y, Honjo T, Kitamura T.
  • Journal Title: Leukemia 24 Pages: 1018-1024
  • Peer Reviewed
• [Journal Article] 免疫グロブリンの体細胞突然変異・クラススイッチとAIDおよびその関連分子 (2010)
  • Author(s): 新蔵礼子
  • Journal Title: 臨床免疫・アレルギー科 54 Pages: 72-79
• [Journal Article] AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model. (2010)
  • Author(s): Komeno Y, Kitaura J, Watanabe-Okochi N, Kato N, Oki T, Nakahara F, Harada Y, Harada H, Shinkura R, Nagaoka H, Hayashi Y, Honjo T, Kitamura T.
  • Journal Title: Leukemia Volume: 24 Pages: 1018-1024
  • Peer Reviewed
• [Journal Article] 免疫グロブリンの体細胞突然変異・クラススイッチとAIDおよびその関連分子 (2010)
  • Author(s): 新蔵礼子
  • Journal Title: 臨床免疫・アレルギー科 Volume: 54 Pages: 72-79
• [Journal Article] Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes. (2009)
  • Author(s): Sabouri Z, Okazaki IM, Shinkura R, Begum N, Nagaoka H, Tsuchimoto D, Nakabeppu Y , Honjo T.
  • Journal Title: International Immunology 21 Pages: 947-955
  • NAID: 10025387710
  • Peer Reviewed
• [Journal Article] B cell-specific and stimulation-responsive enhancers derepress the Aicda gene by overcoming the effects of silencers. (2009)
  • Author(s): Tran TH, Nakata N, Begum NA, Shinkura R, Honjo T, Nagaoka H.
  • Journal Title: Nature Immunology 11 Pages: 148-154
  • Peer Reviewed
• [Journal Article] AID-induced decrease in topoisomerase 1 induces DNA structural alterlation and DNA cleavage for class switch recombination. (2009)
  • Author(s): Kobayashi M, Aida M, Nagaoka H, Begum NA, Kitawaki Y, Nakata M, Stanlie A, Doi T, Kato L, Okazaki IM, Shinkura R, Muramatsu M, Kinoshita K, Honjo T.
  • Journal Title: PNAS 106 Pages: 22375-22380
  • Peer Reviewed
• [Journal Article] The C-terminal region of activation-induced cytidine deaminase is responsible for a recombination function other than DNA cleavage in class switch recombination. (2009)
  • Author(s): Doi T, Kato L, Ito S, Shinkura R, Wei M, Nagaoka Hm, Wang J, Honjoj T.
  • Journal Title: PNAS 106 Pages: 2758-2763
  • Peer Reviewed
• [Journal Article] Molecular mechanism for generation of antibody memory. (2009)
  • Author(s): Shivarov V, Shinkura R, Doi T, BegumNA, Nagaoka H, Okazaki IM, Ito S, Nonaka T, Kinoshita K, Honjo T.
  • Journal Title: Philos Trans R Soc Lond B Bio Sci 364 Pages: 569-575
• [Journal Article] Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes. (2009)
  • Author(s): Sabouri Z, et al.
  • Journal Title: International immunology 21 Pages: 947-955
  • Peer Reviewed
• [Journal Article] B cell-specific and stimulation-responsive enhancers derepress the Aicda gene by overcoming the effects of silencers. (2009)
  • Author(s): Tran TH, et al.
  • Journal Title: Nature Immunology 11 Pages: 148-154
  • Peer Reviewed
• [Journal Article] AID-induced decrease in topoisomerase 1 induces DNA structural alterlation and DNA cleavage for class switch recombination. (2009)
  • Author(s): Kobayashi M, et al.
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 22375-22380
  • Peer Reviewed
• [Journal Article] The C-terminal region of activation-induced cytidine deaminase is responsible for a recombination function other than DNA cleavage in class switch recombination. (2009)
  • Author(s): Doi T., et al.
  • Journal Title: Proc Natl Acad Sci U S A. 106 Pages: 2758-2763
  • Peer Reviewed
• [Journal Article] Molecular mechanism for generation of antibody memory. (2009)
  • Author(s): Shivarov V, et al.
  • Journal Title: Philos Trans R Soc Lond B Bio Sci 364 Pages: 569-575
• [Journal Article] Dissociation of in vitro DNA deamination activity and physiological functions of AID mutants. (2008)
  • Author(s): Shivarov V, Shinkura R, Honjo T.
  • Journal Title: PNAS 105 Pages: 15866-15871
  • Peer Reviewed
• [Journal Article] Dissociation of in vitro DNA deamination activity and physiological functions of AID mutants. (2008)
  • Author(s): Shivarov, V, Shinkura R, Honjo T.
  • Journal Title: Proc Natl Acad Sci U S A. 105 Pages: 15866-15871
  • Peer Reviewed
• [Presentation] Knock-in mice carrying a somatic hypermutation-defective AICDA mutation have compromised mucosal defense and impaired gut homeostasis. (2010)
  • Author(s): Shinkura R, Wei M, Honjo T.
  • Organizer: 14^<th> International Congress of Immunology.
  • Place of Presentation: Kobe, Japan.
  • Year and Date: 2010-08-26
• [Presentation] Knock-in mice carrying a somatic hypermutation-defective AICDA mutation have compromised mucosal defense and impaired gut homeostasis. (2010)
  • Author(s): Shinkura R, Wei M, Honjo T.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-26
• [Presentation] Dissociation of in vitro DNA deamination activity and physiological functions of AID mutants. (2008)
  • Author(s): Shinkura R, Shivarov V, Honjo T.
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] Dissociation of in vitro DNA deamination activity and physiological functions of AID mutants. (2008)
  • Author(s): Shinkura R, Shivarov V, Honjo T.
  • 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: 神戸ポートピアホテル
  • Year and Date: 2008-12-11
• [Remarks] ホームページ等
  • URL: http://www.nagahama-i-bio.ac.jp/news/news/2011/01/post_107.html
• [Remarks]
  • URL: http://www.nagahama-i-bio.ac.jp/news/news/2011/01/post_107.html