title: Humanized SCID mice models of SLE.
abstract: The pathological DNA-specific B cells in Systemic lupus erythematosus are a logical target for a selected therapeutic intervention. It has been recently shown that complement receptor type 1 on human B and T-lymphocytes has suppressive activity. The co-crosslinking of this receptor with the B-cell receptor (BCR) inhibits B cell activation and proliferation and it could be an attractive new target for negative signal delivery. Experimental therapy in humans is limited by many restrictions. Severe combined immunodeficiency (SCID) mice, which lack both T and B lymphocytes and accept xenogenic cells have been used for human cell transfer for evaluating the pathogenesis of human SLE. We hypothesize that it may be possible to re-establish tolerance to native DNA in humanized SCID mice with cells transferred from SLE patients by administering to them a chimeric molecule, containing a monoclonal antibody against human inhibitory complement receptor type 1 coupled to a decapeptide DWEYSVWLSN that mimics DNA antigenically. These protein-engineered molecules are able to co-crosslink selectively the antigen receptors of B-cells possessing anti-native DNA specificity with the inhibitory surface receptors, thus delivering a strong suppressive signal.
authors.affiliation: Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Nikola
authors.initials: N
authors.lastname: Kerekov
authors.forename: Nikolina
authors.initials: N
authors.lastname: Mihaylova
authors.forename: Jozsef
authors.initials: J
authors.lastname: Prechl
authors.forename: Andrey
authors.initials: A
authors.lastname: Tchorbanov
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000188:drug therapy / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D011947:Receptors, Antigen, B-Cell