| Project/Area Number |
20K16283
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49070:Immunology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Koike Takuya 大阪大学, 感染症総合教育研究拠点, 特別研究員 (PD) (10855456)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 免疫記憶 / 記憶B細胞 / 長寿命形質細胞 / ニッチ / 胚中心 |
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| Outline of Research at the Start |
ワクチン応答や再感染時の防御の主体である記憶B細胞の形成・長期生存の機構は未だ不明である。近年、記憶B細胞がリンパ節のB細胞濾胞辺縁部に局在する知見が蓄積されてきている。これらの観察を踏まえ、本研究では今まで報告されていない記憶B細胞の支持細胞・生存因子および記憶B細胞の生存ニッチへの遊走因子を様々な遺伝子改変マウスを用いて同定することを目的とする。その成果は、新規ワクチン療法の開発およびアレルギー・自己免疫疾患等の新たな原因療法の創出に繋がると期待される。
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| Outline of Final Research Achievements |
Immune memory involving B cells consists of memory B cells and long-lived plasma cells, but the mechanism of long-term survival of these cells remains unclear. We found that BAFF is important for the long-term survival of memory B cells. Since there were no molecular markers that could identify long-lived plasma cells, we generated a plasma cell time-stamping mouse system to discriminate long-lived plasma cells based on survival time. Using this system, we found that only small population of the plasma cells that entered the bone marrow enter B220lo MHC-IIlo long-lived plasma cell pool. Furthermore, the short-lived plasma cells were motile and migratory in the bone marrow, while the long-lived plasma cells were immobilized. These observations suggest that plasma cells behavior in BM is dynamically altered during their differentiation to B220loMHC-IIlo long lived plasma cells and that strength or stability of con- tact with the BM niche might be associated with PC longevity.
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| Academic Significance and Societal Importance of the Research Achievements |
長寿命形質細胞の判別方法を明確にし、その形成機構について重要な観察を示した。この知見は長寿命形質細胞の生存機構のより詳細な解析を可能し、長年不明であった免疫記憶の維持機構を解明する手助けになる。これにより、長期に継続するワクチンの開発の一助となると考えられる。
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