T cell-independent immune response and intracellular degradation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19373
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Nihon University (2022-2023); Tokyo Medical and Dental University (2021)
• Principal Investigator: TSUBATA Takeshi 日本大学, 歯学部, 客員教授 (80197756)
• Co-Investigator(Kenkyū-buntansha): スルタン ソフィア・シェリル 東京医科歯科大学, 難治疾患研究所, 非常勤講師 (20838437) ; 沼本 修孝 東京医科歯科大学, 難治疾患研究所, 准教授 (20378582)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 多糖抗原 / デキストラン / B細胞 / 抗体産生 / 細胞内分解

Outline of Final Research Achievements

Polysaccharide antigens activate B cells and induce production of specific antibodies in a manner independent of T cells. However, little is known about how polysaccharides activate B cells. When B cells recognize antigens, antigens are endocytosed and translocated to the endosome/lysosome compartment. Protein antigens are rapidly degraded whereas polysaccharides persist there for a prolonged time. Dextranase that degrade the polysaccharide dextran is a secretary protein expressed by microbes. By fusing dextranase with an animal lysosomal protein, we succeeded in converting dextranase to an animal lysosomal enzyme. Using this enzyme, we showed that persistence of polysaccharides in the endosome/lysosome compartment is crucial for B cell activation induced by polysaccharides.

Free Research Field

免疫学、生化学

Academic Significance and Societal Importance of the Research Achievements

肺炎球菌など莢膜を持つ細菌の莢膜多糖には抗体が産生され、莢膜多糖への抗体がこれら細菌への獲得免疫応答で中心的な役割を果たす。小児や高齢者では多糖抗原への抗体産生が低下するためにこれら感染症に罹患しやすくなる。一方、莢膜多糖を含むワクチンがこれらの感染症の予防に有用である。多糖抗原による抗体産生のメカニズムが明らかになれば、小児や高齢者での多糖抗原への抗体産生低下の予防法の開発や、莢膜を持つ細菌への有効性の高いワクチンの開発につながる。