Identification and Characterization of a Lupus Suppressor 129 Locus on Chromosome 3

被引：12

作者：

Carlucci, Francesco ^{[1
]}

Fossati-Jimack, Liliane ^{[1
]}

Dumitriu, Ingrid E. ^{[1
]}

Heidari, Yasin ^{[1
]}

Walport, Mark J. ^{[1
]}

Szajna, Marta ^{[1
]}

Baruah, Paramita ^{[1
]}

Garden, Oliver A. ^{[3
]}

Cook, H. Terence ^{[2
]}

Botto, Marina ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Rheumatol Sect, London W12 0NN, England

[2] Univ London Imperial Coll Sci Technol & Med, Dept Histopathol, Fac Med, London W12 0NN, England

[3] Univ London Royal Vet Coll, Dept Vet Clin Sci, London, England

来源：

JOURNAL OF IMMUNOLOGY | 2010年 / 184卷 / 11期

基金：

英国惠康基金;

关键词：

T-CELL-ACTIVATION; MARGINAL ZONE; MURINE LUPUS; B-CELLS; SPONTANEOUS AUTOIMMUNITY; AUTOANTIBODY PRODUCTION; SYSTEMIC AUTOIMMUNITY; GENETIC DISSECTION; C57BL/6; MICE; PRONE MICE;

D O I：

10.4049/jimmunol.0901463

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The 129-derived Sle16 is a susceptibility locus for systemic autoimmunity when present on the C57BL/6 (B6) background. Genetic analysis of a (129xB6)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. The Journal of Immunology, 2010, 184: 6256-6265.

引用

页码：6256 / 6265

页数：10

共 30 条

[1]

Increased Foxp3+ CD4+ Regulatory T Cells with Intact Suppressive Activity but Altered Cellular Localization in Murine Lupus [J].