Cell type-specific role of inhibitory IgG Fc receptor IIB in murine lupus

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460493
• 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 (2016); Juntendo University (2014-2015)
• Principal Investigator: LIN QINGSHUN 桐蔭横浜大学, 医用工学部, 客員研究員 (00468589)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ループス腎炎 / 自己免疫寛容破綻 / 細胞特異的FcγRIIB欠損 / B細胞 / 単球/マクロファージ / 樹状細胞 / B細胞活性化因子 / IL-1b,IL-10,CLcf1

Outline of Final Research Achievements

C57BL/6 mice carrying the Yaa autoimmune susceptibility locus spontaneously develop lethal lupus nephritis when the FcγRIIb gene is deleted (B6.FcγRIIb-/-.Yaa). To define the cell type specific role of FcγRIIb in the disease, we established B cell (CD19Cre.Yaa), myeloid cell (C/EBPαCre.Yaa), and dendritic cells (DC) (CD11cCre.Yaa) specific FcγRIIb-deficient B6.Yaa mouse strains. CD19Cre.Yaa mice developed milder lupus nephritis compared to B6.FcγRIIb-/-.Yaa mice, indicating that FcγRIIb deficiency on only B cells is not sufficient for the development of severe disease. Surprisingly, C/EBPαCre.Yaa mice developed similar mild disease as CD19Cre.Yaa mice whereas CD11cCre.Yaa stayed disease free. These observations indicate that, in B6. FcγRIIb-/-.Yaa mice, FcγRIIb deficiency on both B cells and myeloid cells, but not on DCs, contribute to the development of severe lupus with high autoantibody titers.

Free Research Field

基礎医学・実験病理学