Mechanisms underlying long-term survival and immune-modulatory function of plasma cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03503
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Osaka University
• Principal Investigator: ISE Wataru 大阪大学, 感染症総合教育研究拠点, 教授 (70323483)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 抗体 / プラズマ細胞 / 長期生存 / インテグリン

Outline of Final Research Achievements

We analyzed long-term survival of plasma cells in bone marrow, spleen, or gut by using plasma cell fate mapping system. We found that plasma cells survive in bone marrow better than in other tissues with isotype-dependent half-lives. Furthermore, we demonstrated that long-lived plasma cells are B220loMHC-IIlo and are immobilized in the BM environment. Unexpectedly, there was no significant difference in the longevity between pre-GC and post-GC plasma cells. Finally, we analyzed molecular mechanisms by which plasma cells generated in lymphoid tissues migrate to bone marrow and found that the transcription factor KLF2 is required for integrin beta 7 positive plasma cells to migrate to bone marrow.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

プラズマ細胞の長期生存を支える分子機構を解明することは、ワクチン開発のみならず、アレルギーや自己免疫疾患の治療法開発にも重要である。本研究ではプラズマ細胞の生存ニッチとしての骨髄の重要性を確認すると同時に、長寿命プラズマ細胞の骨髄移動の分子メカニズムを初めて明らかにした。また長寿命プラズマ細胞を識別可能なマーカーの同定にも成功した。本研究の成果は、抗体産生応答の持続性に優れたワクチン開発に大きく貢献するものである。