Approach to regulation of an anti-DNA antibody-knock-in mouse nephritis model

Research Project

Project/Area Number	25461473
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Collagenous pathology/Allergology
Research Institution	Kyoto University
Principal Investigator	Yoshifuji Hajime 京都大学, 医学(系)研究科(研究院), 助教 (20422975)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000) Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	膠原病学
Outline of Final Research Achievements	We established a systemic lupus erythematosus nephropathy model, anti-DNA antibody gene (R4A)-knock-in mice. To pursuit autoreactive B cells, we mated normal mice and R4A-knockin mice and obtained WT(a)/R4A(b)-F1 mice, in which we can identify normal B cells by anti-IgM(a) and anti-DNA-antibody-producing B cells by anti-IgM(b) antibodies. As a result, IgM(b)-positive cells were markedly decreased probably by a clonal deletion. RAG genes were markedly upregulated in IgM(b)-positive cells, implying that editing of immunoglobulin light chain was activated. These results elucidated a part of mechanisms how autoreactive B cells were deleted or rescued.