Laboratory of Immunogenetics

Silvia Bolland, Ph.D.

Chief, Autoimmunity and Functional Genomics Section

Description of Research Program

Our group is interested in immune inhibitory pathways and their role in preventing autoimmunity. We have generated a new model for systemic autoimmune disease (Fig.1) 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.

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 (Fig.2). 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 (Fig.3). Our future experiments will explore expression levels of Toll-like receptors and other genetic factors that regulate the development of autoimmunity.

Awards

SLE Foundation, Lupus Research Institute

Research Group Members

Left to right: Prapaporn (Bee) Pisitkun, Tanya Tarasenko, Silvia Bolland, Bethany Scott, Hang Leung, Jonathan Deane, and Hemanta Kole

Selected Publications

(View list in PubMed.)

Deane JA, Bolland, S. Nucleic acid-sensing TLRs as modifiers of autoimmunity. J Immunol. Nov. 2006; 177: 6573-6578.

Pisitkun P, Deane JA, Difilippantonio MJ, Tarasenko T, Satterthwaite AB, Bolland S. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science. 2006 Jun 16;312(5780):1669-72. Epub 2006 May 18.

Bolland S, Yim YS, Tus K, Wakeland EK, Ravetch JV. Genetic modifiers of systemic lupus erythematosus in FcγRIIB(-/-) mice. J Exp Med. 2002 May 6;195(9):1167-74.

Ravetch JV, Bolland S. IgG Fc receptors. Annu Rev Immunol. 2001;19:275-90.

Bolland S, Ravetch J. Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis. Immunity. 2000 Aug;13(2):277-85.

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