Experimental Therapy in Humanized SCID Mice Models of SLE
Andrey Ivanov Tchorbanov
Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Abstract:
The pathological DNA-specific B cells in SLE are a target for therapeutic intervention. The complement receptor (CR1) on human B cells has suppressive activity and co-crosslinking with BCR inhibits cell activation. Experimental therapy in humans is limited by many restrictions. SCID mice, which lack both T and B lymphocytes have been used for human cell transfer for evaluating the pathogenesis of human SLE. We re-established tolerance to native DNA in humanized SLE-SCID mice by administering to them a chimeric molecule, containing an antibody against CR1 coupled to a decapeptide that mimics antigenically DNA. This engineered molecule bounds selectively the immunoglobulin receptors of B-cells with anti-native DNA specificity and deliver selectively to them a suppressive signal. SCID mice were humanized by transfer of PBMC from SLE patients and the animals were injected with the DNA-like chimera. Reconstituted SCID mice showed presence of auto-antibodies, as well as human immunoglobulin deposition in the renal glomeruli. Treatment of the transferred SCID mice with the chimeric molecules prevented appearance of anti-DNA antibodies and proteinuria. The presented transferred SCID model explores a novel approach for preventing autoimmunity. The selective silencing of human autoreactive B cells demonstrates a new therapeutic method for suppressing disease-associated B lymphocytes only.
