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Selective Silencing of DNA-Specific B Lymphocytes Delays Lupus Activity in Mrl/Lpr Mice
Resource
EUROPEAN JOURNAL OF IMMUNOLOGY v.37 n.12 pp.3587-3596
Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Journal Volume
v.37
Journal Issue
n.12
Pages
3587-3596
Date Issued
2007
Date
2007
Author(s)
Tchorbanov, Andrey?I.
Voynova, Elisaveta?N.
Mihaylova, Nikolina?M.
Todorov, Todor?A.
Nikolova, Maria
Yomtova, Vihra?M.
Chiang, Bor-Luen
Vassilev, Tchavdar?L.
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 Fc gamma IIb surface receptors. A hybrid molecule was constructed by coupling the DNA- mimicking DWEYSVWLSN peptide to a monoclonal anti-mouse Fc gamma RIIb antibody. This chimeric antibody was added to cultured spleen cells from sick MRL/1pr 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.
Subjects
autoreactive B cells
Fc gamma IIb receptor
systemic lupus
erythematosus
Type
journal article