Mice immunized with the T-dependent Ag, goat anti-mouse IgD Ab (GaMD), develop mastocytosis and IgE and IgG anti-goat IgG (GIgG) Ab. Surprisingly, these mice develop IgG/FcγRIII-dependent anaphylaxis, but not IgE/FcϵRI/mast cell-dependent anaphylaxis, when challenged with 100 μg of GIgG. Studies were performed to explain the absence of IgE-mediated anaphylaxis.

To test the hypothesis that IgG Ab inhibit IgE-mediated anaphylaxis by blocking GIgG binding to mast cell-associated IgE anti-GIgG Ab, we compared the abilities of 100 vs. 10,000 μg of GIgG to induce mast cell degranulation and anaphylaxis in GaMD-immunized mice in which IgG-dependent anaphylaxis was suppressed by anti-FcγRII/RIII mAb. We also evaluated the ability of polyclonal IgG anti-TNP Ab to suppress TNP-OVA-induced anaphylaxis and mast cell degranulation in IgE anti-TNP mAb-primed mice.

Both 100 and 10,000 μg of GIgG induced anaphylaxis in otherwise untreated GaMD-primed mice, but only the 10,000 μg dose induced mast cell degranulation (histamine and MMCP1 release) and only the 10,000 μg dose induced anaphylaxis in anti-FcγRII/RIII mAb-treated, GaMD-primed mice. Furthermore, IgG anti-TNP Ab blocked TNP-OVA-induced anaphylaxis in mice primed with IgE anti-TNP mAb. Blocking was overcome by increasing the challenge dose of TNP-OVA. Higher doses of Ag were required to induce IgG-mediated anaphylaxis than IgE-mediated anaphylaxis.

IgG Ab can block IgE-mediated anaphylaxis by competing for Ag with mast cell-bound IgE Ab and can protect against anaphylaxis induced by relatively low quantities of Ag. However, challenge with a high Ag dose may both overcome the protective effect of IgG blocking Ab and induce IgG-mediated anaphylaxis.