Lessons from BXSB and related mouse models
| Autor: | Shozo Izui, Nabila Ibnou-Zekri, Liliane Fossati-Jimack, Masahiro Iwamoto |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Immunology
Lupus nephritis Autoimmunity ddc:616.07 Major histocompatibility complex medicine.disease_cause Autoantibodies/biosynthesis Chimera (genetics) Mice Antigen H-2 Antigens/genetics Lupus Erythematosus Systemic/ genetics Y Chromosome medicine Immunology and Allergy Lupus Erythematosus Systemic Animals Humans Genetic Predisposition to Disease Allele skin and connective tissue diseases Autoantibodies Lupus erythematosus biology business.industry Autoantibody H-2 Antigens medicine.disease Antiphospholipid Syndrome Antiphospholipid Syndrome/etiology Disease Models Animal biology.protein business |
| Zdroj: | International Reviews of Immunology, Vol. 19, No 4-5 (2000) pp. 447-472 |
| ISSN: | 0883-0185 |
| Popis: | The BXSB murine strain spontaneously develops an autoimmune syndrome with features of systemic lupus erythematosus (SLE) that affects males much earlier than females, due to the presence of an as yet unidentified mutant gene located on its Y chromosome, designated Yaa (Y-linked autoimmune acceleration). The Yaa gene by itself is unable to induce significant autoimmune responses in mice without an apparent SLE background, while it can induce and accelerate the development of an SLE in combination with autosomal susceptibility alleles present in lupus-prone mice. Although the genes encoded within or closely linked to the MHC locus play an important role in the development or protection of SLE, the MHC effect can be completely masked by the presence of the Yaa gene in mice highly predisposed to SLE. The role of the Yaa gene for the acceleration of SLE is apparently two-fold; it enhances overall autoimmune responses against autoantigens to which mice respond relatively weakly, and promotes Th 1 responses against autoantigens to which mice respond relatively well, leading to the production of more pathogenic autoantibodies, i.e., FcgammaR-fixing IgG2a and cryoglobulin IgG3 autoantibodies. Yaa+ - Yaa- double bone marrow chimera experiments revealed that the Yaa defect is expressed in B cells, but not in T cells, and that T cells from non-autoimmune mice are capable of providing help for autoimmune responses by collaborating Yaa+ B cells. We speculate that the Yaa defect may decrease the threshold for antigen receptor-dependent stimulation, leading to the triggering and excessive stimulation of autoreactive T and B cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|