Lupus resistance is associated with marginal zone abnormalities in an NZM murine model.
Lab Invest
; 87(1): 14-28, 2007 Jan.
Article
en En
| MEDLINE
| ID: mdl-17170739
ABSTRACT
The NZM2410 and NZM TAN (TAN) are two of 27 inbred strains derived from an intercross between the NZW and NZB strains. NZM2410 mice develop a highly penetrant lupus nephritis mediated by three susceptibility loci, Sle1, Sle2 and Sle3. These three loci have been combined on a C57BL/6 background in a triple congenic strain that reconstitutes the NZM2410 autoimmune phenotype. Remarkably, inspite of the presence of Sle1, Sle2 and Sle3, TAN mice display a mild autoimmune phenotype reminiscent of NZW. Contrary to the lupus-prone strains, the majority of TAN CD4(+) T cells are in a naïve-inactivated stage. TAN mice show B-cell developmental abnormalities similar to lupus-prone mice, such an accumulation of transitional T1 cells and peritoneal B-1a cells. TAN mice show, however, a unique expansion of the splenic marginal zone, in which B cells express high levels of CD5 and CD9, fail to migrate to the follicles in response to LPS, and show sub-optimal binding of T-independent type 2 antigens. Therefore, TAN mice present a functional silencing of marginal zone B cells, which have been previously implicated with autoimmune process. The TAN strain thus provides a novel model for the analysis of the genetic determinants of B-cell autoreactivity.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Subgrupos de Linfocitos B
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Repeticiones de Microsatélite
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Predisposición Genética a la Enfermedad
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Lupus Eritematoso Sistémico
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Ganglios Linfáticos
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Ratones Endogámicos
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Lab Invest
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos