Activation mechanism of memory B cell for protection against variant influenza virus infection

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02740
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Ehime University (2022-2023); Osaka University (2021)
• Principal Investigator: Shinnakasu Ryo 愛媛大学, 学術支援センター, 准教授 (00451758)
• Co-Investigator(Kenkyū-buntansha): 井上 毅 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (80466838)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 免疫記憶B細胞 / 変異インフルエンザウイルス

Outline of Final Research Achievements

HA stem specific memory B cells are important for the initial defense against influenza pandemics. In mice with a history of infection, we evaluated the cellular dynamics during immune induction by mutant virus strain and found that the cells that were mainly activated were derived from stem specific memory cells, and in particular, differentiation into plasma cells was induced from the wide range of repertoire in the primary memory cells and into GC cells was induced from some repertoires in the primary memory cells which are presumed with relatively low affinity. And also the results suggest a new induction of affinity maturation within secondary GCs. Regarding the factors that could influence the immune response, the amount of existing memory B cells and the presence of existing antibodies were found to be important.

Free Research Field

感染免疫

Academic Significance and Societal Importance of the Research Achievements

これまでの変異インフルエンザ防御機構に関する基礎的研究については、断片的な研究成果は存在していたものの、１) 変異ウイルス感染防御へのメモリーB細胞の重要性、２)メモリーB細胞の生成・維持および活性化されるメカニズム、という根源的課題にアプローチする研究は実験系構築の難しさから進んでこなかった。申請者はこの問題を解決するため、新規の実験モデルやマウスモデルを独自に構築し本課題にとりかかった。プロジェクト自体は未完で継続中ではあるが、これまでに得られ知見および今後の研究結果から得られる知見は、今後のパンデミック発生に対する予防・治療法開発において生かされていくことが期待できる。