Chronological impact of fetal immune memory on visceral adipose tissue inflammation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02372
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Goitsuka Ryo 東京理科大学, 研究推進機構生命医科学研究所, 教授 (50301552)
• Co-Investigator(Kenkyū-buntansha): 樋上 賀一 東京理科大学, 薬学部生命創薬科学科, 教授 (90253640)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 早期ライフステージ / 免疫系 / B細胞 / 自然抗体

Outline of Final Research Achievements

B-1a B cells have been demonstrated to develop during the embryonic period and play a major role in natural antibody secretion and immune regulation. In the present study, we created a highly efficient temporally controllable RAG2-based lymphoid lineage cell labeling and tracking system to understand the biological properties of B-1a cells generated during the embryonic period. This approach revealed that many B-1a cells with a history of RAG2 expression during the embryonic period persist in the adult B-1a compartment. Furthermore, neonatal depletion of B cells caused the loss of bone marrow IgM+ plasmablasts/plasma cells that had expressed RAG2 during the embryonic period, indicating a continuous replenishment from the adult B-1a cell compartment with RAG2 expression history during the embryonic period. These findings define the importance of B-1a cells generated during the embryonic period for natural IgM production under native hematopoietic conditions.

Free Research Field

基礎獣医学

Academic Significance and Societal Importance of the Research Achievements

腹腔などの脂肪組織に局在するB細胞は胎生期造血系に由来し、広域交差反応性の自然抗体や抑制性サイトカインIL-10を産生することで免疫制御に関与すると考えられてきた。しかしながら、表現型を軸とした既存の解析手法では胎生期B細胞の免疫記憶と成体疾患の直接的な関連性を解析することは不可能であった。本研究で作製した生理的条件での胎生期B細胞の遺伝学的細胞系譜追跡システムを用いた知見はこれまでの胎児肝細胞移入を用いた研究成果を生理的条件で厳密に確定するものであり、今後、内臓脂肪炎症などの免疫疾患における胎生期B細胞の機能解析の応用基盤を構築するものである。