Silvia Bolland, Ph.D.

Fig. 1. We have generated a new model for systemic autoimmune disease in mice deficient in FcγRIIB, an IgG-binding receptor that inhibits antibody production and inflammatory responses.These mice develop a spontaneous disease that resembles lupus in humans, but only in certain genetic backgrounds. We are studying genetic modifiers that augment susceptibility and severity of disease so that we can understand cellular mechanisms that induce these pathologies and identify new genes that can be used as therapeutic targets.

Figure 2a. Addition of the Y chromosome-linked Yaa modifier in the FcγRII-ko lupus model results in aggravated glomerulonephritis and a switch from anti-chromatin to anti-nucleolar autoantibodies.

Figure 2b. Addition of the Y chromosome-linked Yaa modifier in the FcγRII-ko lupus model results in aggravated glomerulonephritis and a switch from anti-chromatin to anti-nucleolar autoantibodies.

Figure 2c. Addition of the Y chromosome-linked Yaa modifier in the FcγRII-ko lupus model results in aggravated glomerulonephritis and a switch from anti-chromatin to anti-nucleolar autoantibodies.

Figure 3. We have shown that the nucleolar specificity of Yaa-derived antibodies is a B-cell-intrinsic feature resulting from a large genomic duplication that includes the TLR7 gene. Our future experiments will explore expression levels of Toll-like receptors and other genetic factors that regulate the development of autoimmunity.