Ability of maturation of antibody affinity

• Project/Area Number: 12470080
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Tokyo University of Science
• Principal Investigator: AZUMA Takachika Research Institute for Biological Sciences, Professor, 生命科学研究所, 教授 (00028234)
• Project Period (FY): 2000 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥8,500,000 (Direct Cost: ¥8,500,000); Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2000: ¥5,600,000 (Direct Cost: ¥5,600,000)
• Keywords: antibody / evolution / somatic hypermutation / BCR / DNA polymerase / memory B cell / Polκ / 抗原受容体 / 相互作用 / 進化 / エントロピー / 親和力 / 結合部位

Research Abstract

Affinity maturation of immune response to T cell dependent antigens proceeded in germinal center through two steps; somatic hypermutation and selection of mutants by antigens. We have attempted the following studies ( 1 ) Identification of cis-acting elements involved in regulation of somatic hypermutation of IgH gene. We found the DNase sensitive regions occurring at 3' of CH genes are responsible for high frequency of mutation of VH genes. ( 2 ) We examined whether DNA polymerase k involves in the induction somatic hypermutation and found that it does not. ( 3 ) Relationship between adaptability and structure of CDR3 loop was investigated. ( 4 ) We developed a simple method for estimation of relative affinity of BCR by FACS. ( 5 ) Thermodynamic and kinetic aspects of antibody evolution.

Research Products

• [Publications] Akiko Terauchi, Katsuhiko Hayashi, Daisuke Kitamura, Yuko Kozono, Noboru Motoyama, Takachika Azuma: "A pivotal role for DNase-sensitive regions 3b and/or 4 in the induction of somatic hypermutation of IgH genes"J. Immunol.. 167. 811-820 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Koji Furukawa, Hiroki Shirai, Takachika Azuma, Haruki Nakamura: "A Role of the Third Complementarity Determining Region in the Affinity Maturation of an Antibody"J. Biol. Chem.. 276. 27622-27628 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Shimizu, Yoichi Shinkai, T.Ogi, H.Ohmori, T.Azuma: "The absence of DNA polymerase κ does not affect the somatic hypermutation of mouse immunoglobulin heavy chain gene"Immunol. Letters. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Shimizu, M.Oda, T.Azuma: "Estimation of the relative affinity of B cell receptor by flow cytometry"J. Immunol. Methods. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Sagawa, M.Oda, M.Ishimura, K.Furukawa, T.Azuma: "Thermodynamic and kinetic aspects of antibody evolution during the immune response to hapten"Molec. Immunol.. 39. 801-808 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Akiko Terauchi, Katsuhiko Hayashi, Daisuke Kitamura, Yuko Kozono, Novoru Motoyama, and Takachika Azuma.: "A pivotal role for DNase-sensitive regions 3b and/or 4 in the induction of somatic hypermutation of IgH genesJ."Immunol. 167. 811-820 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Koji Furukawa, Hiroki Shirai, Takachika Azuma, Haruki Nakamura: "A Role of the Third Complementarity Determining Region in the Affinity Maturation of an Antibody."J. Biol. Chem. 276. 29622-27628 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Shimizu, Yoichi Shinkai, T. Ogi, H. Ohmori, T. Azuma: "The absence of DNA polymerase k does not affect the somatic hypermutation of mouse immunoglobulin heavy chain gene."Immunol. Letters. in press.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Shimizu, M. Oda, T. Azuma: "Estimation of the relative affinity of B cell receptor by flow cytometry."J. Immunol. Methods. in press.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Sagawa, M. oda, M. Ishimura, K. Furukawa, T. Azuma: "Thermodynamic and kinetic aspects of antibody evolution during the immune response to hapten."Molec. Immunol.. 39. 801-808 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T.Shimizu, Y.Shinkai, T.Ogi, H.Ohmori, T.Azuma: "The absence of DNA polymerase κ does not affect the somatic hypermutation of mouse immunoglobulin heavy chain gene"Immunological letters. (in press).
• [Publications] T.Shimizu, M.Oda, T.Azuma: "Estimation of the relative affinity of B cell receptor by flow cytometry"Journal Immunological Methods. (in press).
• [Publications] T.Sagawa, M.Oda, Ishimura, K.Furukawa, T.Azuma: "Thermodynamic and kinetic aspects of antibody evolution during the immune response to hanten"Molecular Immunology. 39. 801-808 (2003)
• [Publications] M.Oda, H.Kozono, H.Mori, T.Azuma: "Evidence of allosteric conformational changes in the antibody constant region upon antigen binding"International Immunology. 15. 417-426 (2003)
• [Publications] E.Sato, K.Hirahara, Y.Wzada, T.Yoshimori, T.Azuma, K.Matuoka: "Chronic inflammation in skin can be induced in IgG transgenic mice by a single challenge of multivalent antigen"Journal Allergy Clinical Immunology. 111. 143-148 (2003)
• [Publications] Oda, M., Azuma.T.: "Reevaluation of stoichiometry and affinity/avidity in interactions between anti-hapten antibodies and mono- or multi-valent antigens"Mol.Immunol.. 37. 1111-1122 (2000)
• [Publications] A.Terauchi, K.Hayashi, D.Kitamura, Y.Kozono, N.Motoyama, T.Azuma: "A pivotal role for Dnase I-Sensitive Regions 3b and/or 4 in the induction of somatic hypermutation of IgH genes"J.Immunol.. 167. 811-820 (2001)
• [Publications] K.Furukawa, H.Shirai, T.Azuma, H.Nakamura: "A role of the third complementarity-determining region in the affinity maturation of an antibody"J.Biol.Chem.. 276. 27622-27628 (2001)