title: Suppression of dsDNA-specific B lymphocytes reduces disease symptoms in SCID model of mouse lupus.
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.
authors: Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences , Sofia , Bulgaria .
authors: Vera
authors: V
authors: Gesheva
authors: Nikola
authors: N
authors: Kerekov
authors: Kalina
authors: K
authors: Nikolova
authors: Nikolina
authors: N
authors: Mihaylova
authors: Todor
authors: T
authors: Todorov
authors: Maria
authors: M
authors: Nikolova
authors: Andrey
authors: A
authors: Tchorbanov
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016513:Mice, SCID; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011292:Premedication; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C499172:Fcgr2b protein, mouse; D016756:Immunoglobulins, Intravenous; D010455:Peptides; D017452:Receptors, IgG; D004247:DNA