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Original Article

Suppression of dsDNA-specific B lymphocytes reduces disease symptoms in SCID model of mouse lupus

, , , , , & show all
Pages 162-172 | Received 09 Oct 2013, Accepted 11 Jan 2014, Published online: 06 Feb 2014
 

Abstract

Self-specific B cells play a main role in the pathogenesis of lupus. This autoimmune disease is characterized by the generation of autoantibodies against self antigens, and the elimination of B and T cells involved in the pathological immune response is a logical approach for effective therapy. We have previously constructed a chimeric molecule by coupling a DNA-mimotope peptides to an anti-CD32 antibody. Using this protein molecule for the treatment of lupus-prone MRL/lpr mice, we suppressed selectively the autoreactive B-lymphocytes by cross-linking B cell receptors with the inhibitory FcγRIIb receptors. This approach was limited by the development of anti-chimeric antibodies in MRL mice. In order to avoid this problem, we established a murine severe combined immunodeficiency lupus model, allowing a long-term chimera therapy. Elimination of the double-stranded DNA-specific B cells by chimera therapy in MRL-transferred immunodeficient mice resulted in inhibition of T cell proliferation and prevented the appearance of IgG anti-DNA antibodies and of proteinuria.

Author contributions

A. T., N. M. and V. G. designed the approach of experiments. V. G., N. K., K. N., T. T. and N. M. performed the experiments. A. T., V. G. and M. N. analyzed the data. N. M., M. N. and A. T. wrote and edited the paper.

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