Human antibodies induce arthritis in mice deficient in the low-affinity inhibitory IgG receptor Fc gamma RIIB.
Document Type
Article
Publication Date
2006
Keywords
Arthritis-Experimental, Arthritis-Rheumatoid, Autoantibodies, Binding-Sites-Antibody, Female, Humans, Injections-Intraperitoneal, Male, Mice-Inbred-C57BL, Mice-Knockout, Receptors-IgG
First Page
275
Last Page
280
JAX Source
J Exp Med 2006 Feb; 203(2):275-80.
Abstract
Rheumatoid arthritis (RA) is a complex autoimmune disease with a poorly understood pathogenesis. The disease is associated with polyclonal B cell activation and the production of autoantibodies (autoAbs), but there is a longstanding controversy as to whether such Abs contribute to, or are secondary to, the pathogenesis of RA. To address the potential pathogenicity of human RA-associated Abs, we developed a passive transfer model involving mice deficient in the low-affinity inhibitory Fc receptor, FcgammaRIIB. We report that plasma or serum from patients with active RA can induce inflammation and histological lesions in FcgammaRIIB-/- mice consistent with arthritis, and that this pathogenic activity is caused by the immunoglobulin G-rich fraction. Our results suggest that humoral autoimmunity can contribute directly to autoimmune arthritis, and that FcgammaRIIB-/- mice are a promising model to evaluate the arthritogenic potential of human autoAbs.
Recommended Citation
Petkova SB,
Konstantinov KN,
Sproule TJ,
Lyons BL,
Awwami MA,
Roopenian DC.
Human antibodies induce arthritis in mice deficient in the low-affinity inhibitory IgG receptor Fc gamma RIIB. J Exp Med 2006 Feb; 203(2):275-80.