Molecular bases enabling various BCR responses

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19424
• 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: The University of Tokyo
• Principal Investigator: Miyake Kensuke 東京大学, 医科学研究所, 教授 (60229812)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: Toll様受容体 / B細胞受容体

Outline of Final Research Achievements

The antigen receptor expressed on B cells (B cell receptor, BCR) induces a variety of responses, from proliferation to activation and cell death. Little is known about the molecular basis of this diversity. We hypothesized that the diversity depends on various forms of BCRs such as BCR alone and the BCR-TLR complex, and that the latter induces survival and proliferation. We expressed BCR and TLR9 in the IL-3-dependent cell line Ba/F3. Using these cells, we investigated whether survival and proliferation could be induced in the absence of IL-3. As a result, survival and proliferation were induced in the presence of both anti-IgM antibody and the TLR9 ligand. This cell line is valuable to study the molecular basis of BCR-induced survival and proliferation.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

B細胞受容体からのシグナルは活性化、増殖、分化など多様なB細胞応答を誘導するがその分子基盤は不明である。応答の多様性を説明する分子基盤として、BCRとTLR9との複合体を解析するための細胞株を確立することに成功した。この細胞を用いることで、BCR-TLR９複合体の形成や活性化に関わる分子の検索などが可能となる。その解析で得られる知見はB細胞の生存・増殖の制御に重要であることが予想される。つまり、抗体産生を誘導するアジュバントの開発やB細胞リンホーマの治療薬開発に資することが期待できる。