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* Department of Immunology and
Department of Medicine, Duke University Medical Center, Durham, NC 27710; and
Department of Biological Sciences, University of Wisconsin, Milwaukee, WI 53201
Rheumatoid arthritis is a systemic autoimmune disease. B cells are likely to play a critical role in arthritis pathogenesis, although it is unclear whether they are necessary for disease induction, autoantibody production, or disease progression. To assess the role of B cells in inflammatory arthritis, B cells were depleted using mouse anti-mouse CD20 mAbs in a mouse model of collagen-induced arthritis. CD20 mAbs effectively depleted mature B cells from adult DBA-1 mice. When B cells were depleted using CD20 mAbs before collagen immunization, there was a delay in disease onset and autoantibody production, with significantly diminished severity of arthritis both clinically and histologically. B cell depletion further delayed disease onset if initiated before, as well as after, collagen immunization. However, in both cases, the eventual reappearance of peripheral B cells triggered autoantibody production and the subsequent development of arthritis in collagen-sensitized mice. By contrast, B cell depletion after collagen immunizations did not have a significant effect on arthritis progression or severity. Thus, disease symptoms were only induced when peripheral B cells and their autoantibody products were present in collagen-immunized mice, documenting a critical role for B cells during the elicitation phase of collagen-induced arthritis. These studies suggest that B cell depletion strategies will be most effective when initiated early in the development of inflammatory arthritis, with sustained B cell depletion required to inhibit the production of isotype-switched pathogenic Abs and the evolution of joint inflammation and destruction.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants CA105001, CA81776, CA96547, and AI56363 and Arthritis Foundation.
2 K.Y. and Y.H. contributed equally to these studies and share first authorship.
3 Address correspondence and reprint requests to Dr. Thomas F. Tedder, Box 3010, Department of Immunology, Duke University Medical Center, Durham, NC 27710. E-mail address: thomas.tedder{at}duke.edu
4 Abbreviations used in this paper: RA, rheumatoid arthritis; RF, rheumatoid factor; CCP, cyclic citrullinated peptide; CIA, collagen-induced arthritis; BM, bone marrow.
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