Analysis of Bach2 expression level-dependent regulation of B cell immune response

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08572
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: Muto Akihiko 東北大学, 医学系研究科, 准教授 (80343292)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: B細胞 / Bach2

Outline of Final Research Achievements

In humoral immune responses, antigen activated B cells differentiate into antibody secreting plasma cells (PCs) to eliminate antigen, or undergo class switch recombination (CSR) of immunoglobulin gene to change the isotype of antibody. Dynamic changes in gene regulatory network (GRN) are the molecular mechanism of these cellular responses. It has been proposed that transcriptional repressor Bach2 is required for controlling the cell fate decisions in activated B cells, the mechanism of this decision making by Bach2 in individual cells remains to be elucidated. This research demonstrated that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling. We also revealed that Bach2 expression levels are the intrinsic factor for determining the fate of B cell development. In B cells, we identified that Bach2 expression levels were negatively regulated in response to activation signals.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

最近、ヒトBACH2変異が要因の免疫不全の症例が初めて報告された。このBACH2変異はアミノ酸置換を伴い、ハプロ不全で症状が現れる。これは、細胞内Bach2タンパク質量が適切に保たれる必要があるという本研究成果と矛盾しない。患者B細胞ではクラススイッチに障害があるという結果も本研究と一致する。したがって、本基礎研究の結果が治療戦略の開発に貢献できる可能性がある。