1. ¹Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA
2. ²Pathology and Laboratory Medicine Service, Malcolm Randall Veterans Administration Medical Center, Gainesville, FL, USA

Correspondence: Dr L Morel, PhD, Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, PO Box 100275, 1600 SW Archer Road, Gainesville, FL 32610-0275, USA. E-mail: morel@ufl.edu

Received 10 August 2006; Revised 7 October 2006; Accepted 8 October 2006; Published online 27 November 2006.

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.