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* Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA 19104;
Department of Chemistry and Biochemistry, University of Sciences in Philadelphia, Philadelphia, PA 19104;
Temple University, Philadelphia, PA 19140;
¶ University of Colorado Denver School of Medicine and National Jewish Medical and Research Center, Denver, CO 80206; and
|| Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104
MRL/lpr mice develop a spontaneous systemic lupus erythematosus-like autoimmune syndrome due to a dysfunctional Fas receptor, with contributions from other less well-defined genetic loci. The removal of B cells by genetic manipulation not only prevents autoantibody formation, but it also results in substantially reduced T cell activation and kidney inflammation. To determine whether B cell depletion by administration of Abs is effective in lupus mice with an intact immune system and established disease, we screened several B cell-specific mAbs and found that a combination of anti-CD79
and anti-CD79β Abs was most effective at depleting B cells in vivo. Anti-CD79 therapy started at 4–5 mo of age in MRL/lpr mice significantly decreased B cells (B220+CD19+) in peripheral blood, bone marrow, and spleens. Treated mice also had a significant increase in the number of both double-negative T cells and naive CD4+ T cells, and a decreased relative abundance of CD4+ memory cells. Serum anti-chromatin IgG levels were significantly decreased compared with controls, whereas serum anti-dsDNA IgG, total IgG, or total IgM were unaffected. Overall, survival was improved with lower mean skin scores and significantly fewer focal inflammatory infiltrates in submandibular salivary glands and kidneys. Anti-CD79 mAbs show promise as a potential treatment for systemic lupus erythematosus and as a model for B cell depletion in vivo.
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 Supported by the Lupus Research Institute, the Arthritis Foundation and the Alliance for Lupus Research, the Lupus Foundation of South New Jersey, the Department of Veterans Affairs, and the National Institutes of Health (Grants R01-AR-34156, U19-AI-46358, R01-AI063626, and R01-DE017590).
2 Address correspondence and reprint requests to Dr. Robert A. Eisenberg, Division of Rheumatology, School of Medicine, University of Pennsylvania, Room 747, BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160. E-mail address: raemd{at}mail.med.upenn.edu
3 Abbreviations used in this paper: SLE, systemic lupus erythematosus; FO, follicular; MZ, marginal zone; NF, newly formed.
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