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.