Relationship among pathogenic IgG doses, IgG clearance rate, and disease activity in FcRn-deficient mice. (A and B) FcRn–/– mice were pretreated with IgM (6.47 mg/g body weight) or HDIG (1 mg/g body weight) and 2 hours later injected i.p. with different doses of anti-mBP180 R530, anti-Dsg1 (PF1), or anti-Dsg3 (PV1). The mice were examined 48 hours after pathogenic IgG injection. Serum anti-mBP180 IgG levels in mice pretreated with IgM (black bars) or HDIG (white bars) were quantified by ELISA. Disease activities in mice pretreated with IgM (dark gray bars) or HDIG (light gray bars) were scored by clinical examination. As expected, higher doses of anti-mBP180 IgG (A), anti-Dsg1 IgG (B), and anti-Dsg3 IgG (data not shown) caused higher levels of pathogenic IgG in circulation and more severe clinical diseases. There was no difference in IgG levels and disease severity between IgM- and HDIG-treated mice at each dose of pathogenic IgG. (C–E) WT and FcRn–/– mice were injected i.p. with different doses of pathogenic IgG, and serum pathogenic IgG levels were assayed by ELISA 48 hours later. 59.1%, 50.6%, and 35.3% decreases (decr.) in anti-mBP180 IgG levels were seen in FcRn–/– compared with WT mice at 25, 50, and 100 doses, respectively (C). Similarly, higher doses of anti-Dsg1 and anti-Dsg3 IgG led to lower rates of IgG degradation (D and E). n = 6.