Fas and Fas Ligand Mutations Inhibit Autoantibody Production in Pristane-Induced Lupus

• DOI: 10.4049/jimmunol.165.2.1036
• Publication Date: 2014-04-22T03:02:33Z
• Authors: Minoru Satoh; Jory P Weintraub; Hideo Yoshida; Victoria M Shaheen; Hanno B Richards; Melody Shaw; Westley H Reeves
• Keywords: Mice, Inbred MRL lpr; 0303 health sciences; Fas Ligand Protein; Membrane Glycoproteins; Immunoglobulins; Ligands; Autoantigens; Lupus Nephritis; Chromatin; Mice, Mutant Strains; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Antibodies, Antinuclear; Immunoglobulin G; Mutation; Immune Tolerance; Animals; Cytokines; Female; Immunosuppressive Agents; Autoantibodies

Abstract Mutations of Fas (lpr) or ligand (gld) cause a limited lupus-like syndrome in B6 mice by interfering with the deletion autoreactive B and/or T cells. A more generalized lupus reminiscent that MRL can be induced nonautoimmune strains pristane, which causes nonspecific inflammatory response peritoneal cavity. We hypothesized that, as mice, lpr and gld mutations might accelerate pristane-treated mice. Pristane-treated developed anti-nRNP/Sm, Su, ribosomal P Abs, but little anti-ssDNA chromatin. In contrast, B6/lpr B6/gld spontaneously anti-ssDNA/chromatin not anti-nRNP/Sm/Su/ribosomal P. Unexpectedly, were highly resistant to induction pristane IgM (2 wk) IgG autoantibodies (6 mo), suggesting intact signaling is necessary. Interestingly, did enhance chromatin Ab production it influence develop setting deficiency. Pristane treatment also decreased lymphoproliferation Increased IL-12 was associated consistently well anti-DNA/chromatin. anti-DNA/chromatin Abs IL-6 overproduction The data strongly support idea different subsets are regulated differentially cytokine stimulation signaling.