B cell maturation in thymi of myasthenia gravis patients

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Osaka University
• Principal Investigator: Kazushiro Takata 大阪大学, 大学院医学系研究科, 招へい教員 (20573223)
• Co-Investigator(Kenkyū-buntansha): 木下 允 大阪大学, 大学院医学系研究科, 特任講師(常勤) (10573222)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 重症筋無力症

Outline of Final Research Achievements

We analyzed single cell RNA Sequencing of thymoma from Myasthenia gravis (MG) patients. Analysis of B cells revealed that memory B cells and plasmablasts were enriched in thymoma from MG patients and B cell maturation normally progressed. No protein expressing specifically in B cells of thymoma from MG patient was determined.
Then, we next analyzed thymic epithelium cells which took major rule in antigen presentation in thymus. Gene-set analysis showed that one of thymic epithelium cells highly express the chemokine CXCL12/SDF-1, which was postulated to form a microenvironment that attracts lymphocytes to the thymoma. Furthermore, these cells expressed neuronal protein such as neurofilament and GABA receptor. This result could suggest pathogenic B cells were induced by these thymic epithelium cells expressing neuronal protein.

Free Research Field

脳神経内科

Academic Significance and Societal Importance of the Research Achievements

重症筋無力症の患者血清を用いた研究はこれまで行われてきたが、血清中に含まれる病原性をもった抗体の産生細胞の分化・成熟についてはこれまで明らかではなかった。本研究において胸腺腫内においてB細胞の活発な分化・成熟が行われていることが示唆されただけでなく、これまであきらかではなかった病原性B細胞を分化させるための抗原提示細胞の可能性のある細胞群が明らかとなった。これらにより抗アセチルコリン受容体抗体産生の重症筋無力症の発症メカニズムの一部が明らかになり、そのことは従来の治療法とはことなった新しい治療法の開発につながる可能性がある。