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, FcγRIIB. We report that plasma or serum from patients with active RA can induce inflammation and histological lesions in FcγRIIB−/− 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 FcγRIIB−/− mice are a promising model to evaluate the arthritogenic potential of human autoAbs.
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20 February 2006
Brief Definitive Report|
February 13 2006
Human antibodies induce arthritis in mice deficient in the low-affinity inhibitory IgG receptor FcγRIIB
Stefka B. Petkova,
Stefka B. Petkova
1The Jackson Laboratory, Bar Harbor, ME 04605
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Konstantin N. Konstantinov,
Konstantin N. Konstantinov
2Department of Internal Medicine, Division of Rheumatology, The University of New Mexico, Albuquerque, NM 87122
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Thomas J. Sproule,
Thomas J. Sproule
1The Jackson Laboratory, Bar Harbor, ME 04605
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Bonnie L. Lyons,
Bonnie L. Lyons
1The Jackson Laboratory, Bar Harbor, ME 04605
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Moheeb Al Awwami,
Moheeb Al Awwami
1The Jackson Laboratory, Bar Harbor, ME 04605
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Derry C. Roopenian
Derry C. Roopenian
1The Jackson Laboratory, Bar Harbor, ME 04605
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Stefka B. Petkova
1The Jackson Laboratory, Bar Harbor, ME 04605
Konstantin N. Konstantinov
2Department of Internal Medicine, Division of Rheumatology, The University of New Mexico, Albuquerque, NM 87122
Thomas J. Sproule
1The Jackson Laboratory, Bar Harbor, ME 04605
Bonnie L. Lyons
1The Jackson Laboratory, Bar Harbor, ME 04605
Moheeb Al Awwami
1The Jackson Laboratory, Bar Harbor, ME 04605
Derry C. Roopenian
1The Jackson Laboratory, Bar Harbor, ME 04605
CORRESPONDENCE Derry C. Roopenian: [email protected]
Received:
September 29 2005
Accepted:
January 06 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2006
J Exp Med (2006) 203 (2): 275–280.
Article history
Received:
September 29 2005
Accepted:
January 06 2006
Citation
Stefka B. Petkova, Konstantin N. Konstantinov, Thomas J. Sproule, Bonnie L. Lyons, Moheeb Al Awwami, Derry C. Roopenian; Human antibodies induce arthritis in mice deficient in the low-affinity inhibitory IgG receptor FcγRIIB . J Exp Med 20 February 2006; 203 (2): 275–280. doi: https://doi.org/10.1084/jem.20051951
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