Identification and Characterization of a Lupus Suppressor 129 Locus on Chromosome 3
| Autor: | Oliver A. Garden, Marta Szajna, Liliane Fossati-Jimack, Yasin Heidari, Marina Botto, Paramita Baruah, H. Terence Cook, Francesco Carlucci, Ingrid E. Dumitriu, Mark Walport |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:6256-6265 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0901463 |
| Popis: | The 129-derived Sle16 is a susceptibility locus for systemic autoimmunity when present on the C57BL/6 (B6) background. Genetic analysis of a (129×B6)F2 cross identified a region from the B6 chromosome 3 (Sle18) with positive linkage to antinuclear Abs. In this study, we have generated a B6 congenic strain harboring the 129 allele of Sle18 and intercrossed this line with the lupus-prone B6.129-Sle16 strain. The presence of the 129-Sle18 allele in the B6.129-Sle16Sle18 double congenic mice suppressed the development of Sle16-mediated autoantibody production and ameliorated the renal pathology. The 129-Sle18 locus rectified the B cell abnormalities detected in the B6.129-Sle16 mice, such as the reduction in the percentage of marginal zone B and B1a cells and the increased number of germinal centers. The B6.129-Sle16Sle18 spleens still displayed an increased percentage of activated T and B cells. However, in the B6.129-Sle16Sle18 strain the percentage of naive T cells was equivalent to that in B6.129-Sle18 and B6 mice and these cells showed a reduced proliferative response to anti-CD3 stimulation compared with B6.129-Sle16 T cells. There was a significant increase in the percentage of CD4+FoxP3+regulatory T cells in all congenic strains. These cells had normal regulatory function when tested in vitro. Thus, 129-Sle18 represents a novel, non-MHC lupus-suppressor locus probably operating as a functional modifier of B cells that, in combination with other factors, leads to lupus resistance. Further characterization of this locus will help to uncover the immune mechanism(s) conferring protection against lupus. |
| Databáze: | OpenAIRE |
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