Suppression of dsDNA-specific B lymphocytes reduces disease symptoms in SCID model of mouse lupus
| Autor: | Andrey Tchorbanov, Vera Gesheva, Nikola Kerekov, Maria Nikolova, Kalina Nikolova, Nikolina Mihaylova, Todor A. Todorov |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Mice Inbred MRL lpr Adoptive cell transfer Premedication T-Lymphocytes T cell Kidney Glomerulus Immunology B-cell receptor Mice SCID Lymphocyte Activation Mice Immune system medicine Animals Humans Lupus Erythematosus Systemic Immunology and Allergy skin and connective tissue diseases Cell Proliferation Autoimmune disease B-Lymphocytes Severe combined immunodeficiency Lupus erythematosus biology Receptors IgG Antibodies Monoclonal Immunoglobulins Intravenous DNA medicine.disease Adoptive Transfer Disease Models Animal medicine.anatomical_structure biology.protein Female Antibody Peptides Signal Transduction |
| Zdroj: | Autoimmunity. 47:162-172 |
| ISSN: | 1607-842X 0891-6934 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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