The Role of TLR3 in the Development of Lupus-like Autoimmunity in B6.NZBc13 Mice

The New Zealand Black (NZB) mouse chromosome 13 (c13) is linked to development of autoimmunity. B6 mice containing a portion of NZBc13 (B6.NZBc13 (c13)) develop a lupus phenotype that includes: autoantibody production, increased B and T cell activation, and marginal zone B cell and myeloid dendritic cell expansions. c13 mice have a B cell intrinsic dsRNA-sensing defect, leading to increased TLR3 expression and survival. The role of the aberrant dsRNA sensing in the generation of the c13 autoimmune phenotype was assessed by generating c13 mice with TLR3 knocked out (c13.TLR3KO). Marginal zone B cell expansion and B cell activation were attenuated in c13.TLR3KO mice, but other cellular phenotypes were not affected. Autoantibody production was partially reduced. These results indicate that altered dsRNA-sensing contribute to a portion of the altered cellular phenotypes in c13 mice, but that other susceptibility loci in the c13 interval are required for full development of autoimmunity.MAS