Role of FcgRIIB for autoantibody production inside and outside of germinal centers

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Toin University of Yokohama
• Principal Investigator: Hirose Sachiko 桐蔭横浜大学, 医用工学部, 客員研究員 (00127127)
• Co-Investigator(Renkei-kenkyūsha): AMANO Hirofumi 順天堂大学, 医学部, 准教授 (50318474) ; NISHIMURA Hiroyuki 桐蔭横浜大学, 医用工学部, 教授 (60189313)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: FcγRIIB / Yaa / 自己抗体 / ループス腎炎 / 細胞特異的遺伝子欠損 / 単球 / RNA sequencing

Outline of Final Research Achievements

FcγRIIB-/-.Yaa mice develop severe lupus nephritis with high serum levels of autoantibodies. To determine cell type-specific role of FcγRIIB for autoantibody production, we established B cell-specific FcγRIIB-deficient 　 CD19Cre.Yaa and myeloid cell-specific FcγRIIB-deficient C/EBPαCre.Yaa mice. In CD19Cre.Yaa mice, FcγRIIB-deficient B cells were spontaneously activated in both inside and outside of germinal centers (GCs). In contrast, in C/EBPαCre.Yaa mice, activated B cells were located typically in GCs but not outside GCs. RNA sequencing analysis revealed that B cell activation in C/EBPαCre.Yaa mice was due to the increased production of B cell-stimulating cytokines by activated Gr-1- monocytes, because FcγRIIB-deficient monocytes were activated and differentiated from Gr-1+ into Gr-1- phenotype subset, the latter showed high potential to produce B cell-stimulating cytokines.

Free Research Field

免疫学、病理学