title: Lupus resistance is associated with marginal zone abnormalities in an NZM murine model.
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.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610-0275, USA.
authors.forename: Biyan
authors.initials: B
authors.lastname: Duan
authors.forename: Byron P
authors.initials: BP
authors.lastname: Croker
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007672:Kidney Cortex / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains / Q000235:genetics* / Q000276:immunology; D018895:Microsatellite Repeats / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G