title: Constitutive overexpression of BAFF in autoimmune-resistant mice drives only some aspects of systemic lupus erythematosus-like autoimmunity.
abstract: OBJECTIVE
  To determine whether overexpression of BAFF can promote systemic lupus erythematosus (SLE)-like autoimmunity in mice that are otherwise autoimmune-resistant.
  
  
  METHODS
  We used class II major histocompatibility complex (MHC)-deficient C57BL/6 (B6) mice as a model of resistance to SLE and Sles1-bearing B6 mice as a model of resistance to the autoantibody-promoting capacity of the Sle1 region. We generated BAFF-transgenic (Tg) counterparts to these respective mice and evaluated lymphocyte phenotype, serologic autoimmunity, renal immunopathology, and clinical disease in the BAFF-Tg and non-Tg mouse sets.
  
  
  RESULTS
  Although constitutive BAFF overexpression did not lead to B cell expansion in class II MHC-deficient B6 mice, it did lead to increased serum IgG autoantibody levels. Nevertheless, renal immunopathology was limited, and clinical disease did not develop. In B6 and B6.Sle1 mice, constitutive BAFF overexpression led to increased numbers of B cells and CD4+ memory cells, as well as increased serum IgG and IgA autoantibody levels. Renal immunopathology was modestly greater in BAFF-Tg mice than in their non-Tg counterparts, but again, clinical disease did not develop. Introduction of the Sles1 region into B6.Sle1.Baff mice abrogated the BAFF-driven increase in CD4+ memory cells and the Sle1-driven, but not the BAFF-driven, increase in serum IgG antichromatin levels. Renal immunopathology was substantially ameliorated.
  
  
  CONCLUSIONS
  Although constitutive BAFF overexpression in otherwise autoimmune-resistant mice led to humoral autoimmunity, meaningful renal immunopathology and clinical disease did not develop. This raises the possibility that BAFF overexpression, even when present, may not necessarily drive disease in some SLE patients. This may help explain the heterogeneity of the clinical response to BAFF antagonists in human SLE.
authors.affiliation: Division of Rheumatology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. stohl@usc.edu
authors.forename: William
authors.initials: W
authors.lastname: Stohl
authors.forename: Noam
authors.initials: N
authors.lastname: Jacob
authors.forename: Shunhua
authors.initials: S
authors.lastname: Guo
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology; D053264:B-Cell Activating Factor / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D001323:Autoantibodies; D053264:B-Cell Activating Factor; C505720:Tnfsf13b protein, mouse