title: CD19 hyperexpression augments Sle1-induced humoral autoimmunity but not clinical nephritis.
abstract: OBJECTIVE
  B cell hyperactivity is a common denominator in murine and human systemic lupus erythematosus. Some susceptibility genes in lupus are associated with B cell hyperactivity, but others are clearly not. While the Sle1 lupus susceptibility locus of NZM2410/NZW origin leads to chromatin-focused autoimmunity, genetically engineered overexpression of CD19 leads to "generalized" B cell hyperactivity. We undertook this study to determine the degree to which generalized B cell hyperactivity can amplify lupus pathogenesis.
  
  
  METHODS
  To elucidate the impact of generalized B cell hyperactivity on Sle1-triggered autoimmunity, B6 mice bearing the human CD19 transgene were rendered congenic for the Sle1(z) genetic locus and phenotyped for serologic, cellular, and pathologic evidence of lupus.
  
  
  RESULTS
  As expected, B6.Sle1.hCD19(Tg/Tg) mice, homozygous at Sle1 and bearing the hCD19 transgene, exhibited high levels of IgM and IgG anti-DNA/antiglomerular autoantibodies, skewed B cell subsets, and profoundly activated B and T cells. Despite exhibiting glomerular IgM, IgG, and complement deposits, these mice did not exhibit accelerated mortality or any clinical evidence of renal dysfunction.
  
  
  CONCLUSIONS
  Generalized B cell hyperactivity may augment humoral autoimmunity, but this may not suffice to engender end-organ disease in lupus. These findings allude to the presence of an additional distal checkpoint that dissociates pathogenic autoantibody formation and renal immunoglobulin deposition from the progression to clinical nephritis in lupus.
authors.affiliation: University of Texas Southwestern Medical School, Dallas, TX 75390-8884, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Shi
authors.forename: Chun
authors.initials: C
authors.lastname: Xie
authors.forename: Sooghee
authors.initials: S
authors.lastname: Chang
authors.forename: Xin J
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Thomas
authors.initials: T
authors.lastname: Tedder
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
mesh_terms: D000818:Animals; D000917:Antibody Formation; D018941:Antigens, CD19 / Q000096:biosynthesis*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004843:Epistasis, Genetic; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D009393:Nephritis / Q000235:genetics* / Q000276:immunology*
chemical_list: D018941:Antigens, CD19