IgG immune complexes promote systemic lupus erythematosus by elevating BAFF and inducing T cell infiltration into the glomeruli (P4036)

Abstract

Abstract In systemic lupus erythematosus, the presence of autoantibodies, and the formation of immune complexes are closely related to disease pathogenesis. Although the deposition of immune complexes in the kidneys is a characteristic of SLE, the impact of immune complexes during the onset of disease remains unclear. Here, we show that FcγR/IgG-bound immune complexes containing nuclear self-antigens are displayed on DCs and MFs from C57BL/6 mice at low levels (3-fold), while increased in MRL/lpr mice (10-15 fold). To investigate the biological function of accumulated IgG-immune complexes, we developed a passive antibody transfer system using AID-/-MRL/lpr mice. When treated with anti-nucleosome antibody (IgG), AID-/-MRL/lpr mice accumulated IgG-immune complexes on DCs and MFs, coincident with a dramatic increase in the numbers of splenic B cells, BAFF-secreting DCs, and serum autoantibody titers. The mice also developed lupus nephritis reminiscent of MRL/lpr mice, and showed infiltration of T cells into the glomeruli. These effects were not observed in MRL/lpr mice lacking FcγRI. Our data suggest a mechanistic link between IgG-immune complexes, BAFF secretion, and glomerular infiltration of immune cells. To investigate the role of BAFF in autoimmunity and T cell infiltration into the glomeruli, we will partially neutralize BAFF to restore serum BAFF levels to that of non-diseased mice. This will allow us to define the role of BAFF in autoimmunity, and lupus nephritis.