Selective silencing of autoreactive B lymphocytes-Following the Nature's way.
A novel approach for the selective silencing of targeted autoreactive B lymphocytes is reviewed that mimics the physiological mechanisms for suppressing B cell activity. It is based on the use of bi- or tri-specific chimeric antibodies that cross-link BCRs with a pre-selected antigen-binding specificity with one or more inhibitory types of receptors on the surface of the same disease-associated B lymphocyte. The effect of these engineered antibodies was proved to be specific as they only suppressed the production of the targeted pathological antibodies while sparing those with other specificities. The administration of the chimeric molecules to lupus-prone MRL/lpr mice resulted in decreased levels of disease-associated IgG autoantibodies and of proteinuria, in the prevention of cutaneous lesions, in decreased sizes of the lymphoid organs and in prolonged survival. These results prove that it is indeed possible to selectively silence unwanted B lymphocytes as well as to significantly delay the natural course of a spontaneous antibody-mediated autoimmune disease.
Nikolova
Kalina A
KA
Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Mihaylova
Nikolina M
NM
Voynova
Elisaveta N
EN
Tchorbanov
Andrey I
AI
Voll
Reinhard E
RE
Vassilev
Tchavdar L
TL
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology* / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D001323:Autoantibodies; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2