Selective silencing of DNA-specific B lymphocytes delays lupus activity in MRL/lpr mice |
| |
Authors: | Tchorbanov Andrey I Voynova Elisaveta N Mihaylova Nikolina M Todorov Todor A Nikolova Maria Yomtova Vihra M Chiang Bor-Luen Vassilev Tchavdar L |
| |
Affiliation: | Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. |
| |
Abstract: | The pathological DNA-specific B lymphocytes in lupus are logical targets for a selected therapeutic intervention. We have hypothesized that it should be possible to suppress selectively the activity of these B cells in lupus mice by administering to them an artificial molecule that cross-links their surface immunoglobulins with the inhibitory FcgammaIIb surface receptors. A hybrid molecule was constructed by coupling the DNA-mimicking DWEYSVWLSN peptide to a monoclonal anti-mouse FcgammaRIIb antibody. This chimeric antibody was added to cultured spleen cells from sick MRL/lpr mice, immunized with diphtheria toxoid, resulting in reduction of the numbers of anti-DNA but not of anti-diphtheria IgG antibody-producing cells. Intravenous infusions with the DNA-peptide antibody chimera to 7-wk-old animals prevented the appearance of IgG anti-DNA antibodies and of albuminuria in the next 2 months. The administration of the DNA-peptide chimeric antibody to 18 wk-old mice with full-blown disease resulted in the maintenance of a flat level of IgG anti-DNA antibodies and in delay of the aggravation of the lupus glomerulonephritis. The use of chimeric antibodies targeting inhibitory B lymphocyte receptors represents a novel approach for the selective suppression of autoreactive disease-associated B cells in autoimmune diseases. |
| |
Keywords: | Autoreactive B cells FcγIIb receptor Systemic lupus erythematosus |
本文献已被 PubMed 等数据库收录! |