Regulatory mechanism(s) of CD77-meidated BCR activation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06074
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Fujita Health University
• Principal Investigator: Takematsu Hiromu 藤田医科大学, 医療科学部, 教授 (80324680)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: B細胞 / 胚中心 / 獲得免疫 / 糖脂質 / シグナル伝達

Outline of Final Research Achievements

CD77 is a glycosphingolipid molecule induced in the germinal center B cells. CD77 has been used to mark activated B cells in the germinal centers, very important microenvironment arose in the secondary lymphoid organs such as lymph nodes during acquired immunity response to T-cell dependent antigens. CD77 is biosynthesized from lactosylceramide with A4GALT reaction, transferring galactose in alpha1-4 linkage. We developed model B cell system, in which only glycosphingolipid species are differently expressed due to the introduction of various A4GALT cDNA or control vector. Using this cellular model, effect of CD77 on the B cell antigen receptor (BCR) signaling, activation signal for B cells exposed to the antigen for clonal selection, was analyzed. CD77 regulated CD19, a adaptor molecule downstream of BCR, activating PI3Kinase and PH-domain regulated serine/threonine protein kinases such as PDK1 and Akt1. For such regulation, CD19 glycan played important role.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

胚中心においてＢ細胞は活性化して、抗原特異的な獲得免疫応答がおこる。そのため、胚中心でのＢ細胞活性化の制御が、獲得免疫応答の制御であるとも言える。本研究では、これまで機能的な裏付けはないものの、胚中心B細胞の検出に用いられてきたCD77の機能的な解析を行った。CD77はBCRシグナル伝達制御因子であり、その制御がシグナル伝達におけるアダプター分子として働くCD19を介する者であることを明らかとした。CD19の糖鎖がその制御活性に関わる事など新たな制御機構の解明にも繋がったので、獲得免疫応答の制御に関わる重要な知見であると言える。