Orchestration of memory B cell differentiation controlled by the regulation of IRF4 protein degradation

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19026
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: Ochiai Kyoko 東北大学, 医学系研究科, 助教 (10455785)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 細胞分化 / 転写因子

Outline of Final Research Achievements

In this study, we focused on the molecular mechanism how transcription factors Bach2 and IRF4 regulate cell status between memory B cell and plasma cell. Importantly, Bach2 maintains memory B cell status and represses plasma cell differentiation. We found that IRF4 protein amount was robustly accumulated in Bach2-deficient mouse splenic B cells. Considering that high protein amount of IRF4 promotes plasma cell differentiation, it is suggested that Bach2 controls differentiation by regulating IRF4 protein stability. Since protein stability is often regulated by post-translational modification under signaling pathways, we analyzed post-translational modification of IRF4 upon differentiation stimuli. Furthermore, we identified Bach2 target genes which include signaling molecules. These data suggest that Bach2 is required for the decision whether cell maintains memory B cell status or differentiates to plasma cell by modulating IRF4 protein stability.

Free Research Field

血球系細胞分化制御