Role of FcgRIIB for autoantibody production inside and outside of germinal centers
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 |
Section | 一般 |
Research Field |
Experimental pathology
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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)
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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)
|
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 |
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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Report
(4 results)
Research Products
(27 results)
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[Journal Article] A restricted role for FcγR in the regulation of adaptive immunity.2018
Author(s)
②Fransen MF, Benonisson H, van Maren WW, Sow HS, Breukel C, Linssen MM, Claassens JWC, Brouwers C, van der Kaa J, Camps M, Kleinovink JW, Vonk KK, van Heiningen S, Klar N, van Beek L, Van Harmelen V, Daxinger L, Nandakumar KS, Holmdar R, Coward C, Lin Q, Hirose S, et al.
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Journal Title
J. Immunol.
Volume: 200
Issue: 8
Pages: 2615-2626
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] IL-6 signal blockade ameliorates the enhanced osteoclastogenesis and the associated joint destruction in a novel FcγRIIB-deficient rheumatoid arthritis mouse model.2015
Author(s)
Ohtsuji M, Lin Q, Nishikawa K, Ohtsuji N, Okazaki H, Tsurui H, Amano H, Shirai T, Nishimoto N, Nishimura H, and Hirose S.
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Journal Title
Mod. Rheumatol.
Volume: 25
Issue: 2
Pages: 270-277
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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