Pathophysiological role of B cell subtypes that change with age

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02753
• 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: Kyushu University
• Principal Investigator: Baba Yoshihiro 九州大学, 生体防御医学研究所, 教授 (20415269)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: B細胞 / ABCs / 自己免疫疾患

Outline of Final Research Achievements

We have identified Fcrl5 as a gene that is highly expressed in CD11c+ age-associated B cells. We conducted an analysis using B cell-specific transgenic mice with Fcrl5 (Fcrl5-BTg), and the results showed that these mice spontaneously develop autoimmune diseases with age. Additionally, we found that imiquimod-induced SLE-like autoimmune disease was more severe in Fcrl5-BTg mice compared to wild-type mice. Mechanistically, using a B cell anergy model of HEL-BCR/sHEL, we discovered that increased expression of Fcrl5 led to anergy break. Given that Fcrl5 expression is normally low in asymptomatic B cells, the abnormally elevated Fcrl5 expression may disrupt B cell immune tolerance and contribute to the development of autoimmune diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

免疫老化の研究は、加齢の影響を大きく受ける臓器が胸腺であることから、T細胞老化の研究が精力的に行われている一方で、液性免疫を司るB細胞に関する知見は極めて乏しい。加齢に関連したB細胞サブタイプとして唯一報告されている加齢性B細胞は、その病原性や分化の仕組みは不明である。CD11c+加齢性B細胞に発現が高いFcrl5が、自己反応性B細胞の活性化を誘導することを示す我々の知見は、今後、自己免疫疾患の病態の理解や新規治療候補となる可能性がある。