Analysis of functions of LUBAC in B1 cell development

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08880
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Tohoku Medical and Pharmaceutical University (2018-2020); Kyoto University (2017)
• Principal Investigator: Sasaki Yoshiteru 東北医科薬科大学, 医学部, 助教 (80323004)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 免疫学 / シグナル伝達 / 発生・分化

Outline of Final Research Achievements

Linear polyubiquitin chains are generated specifically by the ubiquitin ligase complex LUBAC. LUBAC is composed of one catalytic subunit, HOIP and two accessary subunits, HOIL-1L and SHARPIN. Linear polyubiquitin chains are known to play important roles in activation of NF-κB and inhibition of programed cell death including apoptosis and necroptosis by TNF stimulation. In this study I analyzed the role of LUBAC in B1 cell development. B1 cells are subdivided into B1a (CD5+) and B1b (CD5-) cells according to CD5 expression. LUBAC is required for the development of both B1a and B1b cells. In this study I found that deletion of RIP3, a critical regulator of necroptosis rescued the development of B1b cells but not B1a cells. This data shows that LUBAC controls B1a and B1b cell development in a different manner.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義としては、これまで不明な点が多かったB1a細胞とB1b細胞の発生機構の違いを明らかにした点が挙げられる。