Thrombocytopenia was not detected in FcRn-deficient neonates delivered from immunized female β3^−/−FcRn^−/− mice bred with β3^+/+FcRn^−/− males. (A) Anti-β3 integrin antibodies were generated in β3^−/−FcRn^−/− mice after 2 immunizations with β3^+/+FcRn^−/− platelets. Antibodies were detected after immunization (black line), during pregnancy (gray line), and immediately after delivery (dotted line). This figure is representative of at least 3 individual experiments. (B) Thrombocytopenia was not detected in heterozygous pups delivered from immunized β3^−/−FcRn^−/− mothers (transfused twice with β3^+/+FcRn^−/− platelets) bred with β3^+/+FcRn^−/− males. FNIT was induced in pups delivered from mothers immunized twice with β3^−/−FcRn^+/+ platelets and bred with β3^+/+FcRn^+/+ males. Pups delivered from naive β3^−/−FcRn^+/+ female mice bred with male β3^+/+FcRn^+/+ mice were used as controls. n = 8-21 for each group. (C) Circulating anti-β3 integrin and platelet-associated IgG were undetectable in β3^−/+FcRn^−/− pups delivered from immunized β3^−/−FcRn^−/− mothers, but detected in β3^−/+FcRn^+/+ pups delivered from immunized β3^−/−FcRn^+/+ mothers. (D) Various IgG isotypes only crossed the FcRn-positive placenta. Mouse anti–mouse β3 integrin mAbs (50 μg; isotypes: JAN DI/IgG₁, PSI EI/IgG_2b, and DEC AI/IgG₃) were injected intraperitoneally into pregnant β3^−/−FcRn^+/+ and β3^−/−FcRn^−/− mice, respectively. After delivery, sera from pups were incubated with β3^+/+ platelets at a 1:5 dilution and stained with goat anti–mouse FITC-conjugated IgG₁, IgG2_b, and IgG₃. n = 6-14 for each group.