Title

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

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.