OBF-1 is essential for the generation of antibody-secreting cells and the development of autoimmunity in MRL-lpr mice.
As reported previously, the lack of the transcriptional co-activator OBF-1 prevented development of autoimmunity in Aiolos knockout mice. To further investigate the role and mechanism of OBF-1 in autoimmunity, we crossed OBF-1 null mice with MRL-lpr mice and generated OBF-1-deficent MRL-lpr mice. OBF-1 deletion abrogated all autoantibodies in the MRL-lpr mice, including anti-dsDNA Ab and anti-Sm Ab. The failure to produce autoantibodies was not related to development of immature or mature B cells, but correlated with severely reduced antibody-secreting cells (ASCs). The loss of OBF-1 protected against hypergammaglobulinemia, immune complex deposition, glomerulonephritis, and early mortality in MRL-lpr mice. In addition, accumulation of CD4(-)CD8(-)B220(+)CD3(+) T cells that characteristically develop in Fas mutation mice were markedly reduced in MRL-lpr mice without OBF-1. These results identify OBF-1 as a critical gene in the development of autoantibodies and reveal an essential role for OBF-1 in the generation of antibody/autoantibody-secreting cells in vivo.
Zuo
Jinxin
J
Health Science Institute, Shanghai Institutes for Biological Sciences & Shanghai JiaoTong University School of Medicine, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China.
Ge
Hailiang
H
Zhu
Guoqiang
G
Matthias
Patrick
P
Sun
Jian
J
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology*; D000936:Antigen-Antibody Complex; D001323:Autoantibodies / Q000096:biosynthesis*; D015551:Autoimmunity / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology; D006942:Hypergammaglobulinemia / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators