| Project/Area Number |
20K05231
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 27040:Biofunction and bioprocess engineering-related
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| Research Institution | Okayama University |
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Principal Investigator |
Kanayama Naoki 岡山大学, ヘルスシステム統合科学学域, 准教授 (70304334)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 抗体 / 親和性成熟 / 抗原受容体 / B細胞抗原レセプター / DT40 / affinity / antibody / B cell receptor / 抗原レセプター / カルシウムシグナル / 親和性 |
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| Outline of Research at the Start |
申請者は、抗体遺伝子への自発的な変異能力を有するニワトリB細胞株DT40を利用して、生体内抗体産生系を模倣したin vitro抗体作製技術を構築した。本研究では、抗原レセプターと抗原との親和性に依存したシグナル調節機構を明らかにして、生体内の抗体産生系の新規な細胞選択機構を見いだす。これを応用して抗原レセプターシグナルの強度を細胞生存シグナルの強度に変換し、生体内での高親和性抗体の超効率的な選択機構を模倣する技術を開発する。この技術をin vitro抗体作製技術に実装し、抗体医薬などの実用抗体の改良に応用する。
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| Outline of Final Research Achievements |
Using the chicken B cell line DT40, which has the ability to spontaneously mutate to antibody genes, we have been constructing an in vitro antibody generation technology that mimics an in vivo antibody generation system. In the course of this work, we found that there are genes whose expression levels change in response to the signal intensity elicited, depending on the affinity of antigen binding to the antigen receptor. In this study, we found genes whose expression depends on the affinity between the antigen receptor and the antigen, and affinity-dependent signaling mechanisms that are assumed to regulate their expression. By applying these findings, we believe that it is possible to develop a technology to convert the intensity of antigen receptor signals into the intensity of cell survival signals and to mimic the efficient selection mechanism of high affinity antibodies in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、B細胞の抗原レセプターシグナル伝達系が抗原との親和性の強弱を区別する機構に関して重要な知見となる。また、本研究の成果は、こうした生体内の高親和性抗体産生機構の理解だけでなく、効率的な抗体作製技術の開発にも重要である。
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