Aging CD19-hBtk mice develop systemic autoimmune disease. (A) Serum Ig concentrations of the indicated isotypes in 10- to 14-week-old CD19-hBtk mice and nontransgenic littermates, as determined by ELISA. (B) Antinuclear IgG autoantibodies, detected by HEp2 reactivity, in serum samples from CD19-hBtk mice and nontransgenic littermates, as well as serum from diseased MRL/lpr mice as reference (objective 40×). Percentages indicate proportion of animals (n = 5-8 per group) with antinuclear IgG autoantibodies. (C) Serum IgG antinucleosome and anti-dsDNA autoantibody levels in the indicated mice quantified by ELISA. Each symbol represents an individual mouse. (D) Glomerular deposition of immune complexes (red) of the indicated IgG isotypes, detected by immunohistochemistry on kidney tissue sections from old (> 40 weeks) CD19-hBtk and WT (WT) littermates. Lower panels show a PAS staining on kidneys from these mice. Dashed lines encircle individual glomeruli (objective 40×). Data are representative of 5 to 8 CD19-hBtk mice.