| Project/Area Number |
15K08432
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Toin University of Yokohama |
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Principal Investigator |
Hirose Sachiko 桐蔭横浜大学, 医用工学部, 客員研究員 (00127127)
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| 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)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| 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 / 全身性エリテマトーデス / 自己抗体産生B細胞 / 抑制性IgG Fc受容体 / リンパ濾胞胚中心 / Yaa変異遺伝子 / 抑制性igG Fc受容体 / 胚中心 |
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| 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.
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