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* Department of Immunology/Microbiology,
Department of Internal Medicine, Section of Rheumatology, and
Department of Orthopedic Surgery, Section of Biochemistry and Molecular Biology, Rush University, Medical Center, Chicago, IL 60612
Depletion of B cells in rheumatoid arthritis is therapeutically efficacious. Yet, the mechanism by which B cells participate in the inflammatory process is unclear. We previously demonstrated that Ag-specific B cells have two important functions in the development of arthritis in a murine model of rheumatoid arthritis, proteoglycan (PG)-induced arthritis (PGIA). PG-specific B cells function as autoantibody-producing cells and as APCs that activate PG-specific T cells. Moreover, the costimulatory molecule CD86 is up-regulated on PG-specific B cells in response to stimulation with PG. To address the requirement for CD80/CD86 expression on B cells in the development of PGIA, we generated mixed bone marrow chimeras in which CD80/CD86 is specifically deleted on B cells and not on other APC populations. Chimeras with a specific deficiency in CD80/CD86 expression on B cells are resistant to the induction of PGIA. The concentration of PG-specific autoantibody is similar in mice sufficient or deficient for CD80/86-expressing B cells, which indicates that resistance to PGIA is not due to the suppression of PG-specific autoantibody production. CD80/86-deficient B cells failed to effectively activate PG-specific autoreactive T cells as indicated by the failure of T cells from PG-immunized CD80/86-deficient B cell chimeras to transfer arthritis into SCID mice. In vitro secondary recall responses to PG are also dependent on CD80/86-expressing B cells. These results demonstrate that a CD80/86:CD28 costimulatory interaction between B cells and T cells is required for autoreactive T cell activation and the induction of arthritis but not for B cell autoantibody production.
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1 This study was supported by National Institutes of Health Grant AR47657 (to A.F.) and by additional support from Robert Burnstine.
2 S.K.O. and Y.C. contributed equally to this study.
3 Address correspondence and reprint requests to Dr. Alison Finnegan, Department of Medicine, Section of Rheumatology, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612. E-mail address: Alison_Finnegan{at}rush.edu
4 Abbreviations used in this paper: RA, rheumatoid arthritis; PG, proteoglycan; DC, dendritic cell; PGIA, proteoglycan-induced arthritis; WT, wild type.
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  K. Hamel, P. Doodes, Y. Cao, Y. Wang, J. Martinson, R. Dunn, M. R. Kehry, B. Farkas, and A. Finnegan Suppression of Proteoglycan-Induced Arthritis by Anti-CD20 B Cell Depletion Therapy Is Mediated by Reduction in Autoantibodies and CD4+ T Cell Reactivity J. Immunol., April 1, 2008; 180(7): 4994 - 5003. [Abstract] [Full Text] [PDF]
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