Monoclonal antibodies to immunoglobulin G₄ induce histamine release from human basophils in vitro

Monoclonal murine antibodies to human IgE, IgG₁, IgG₂, IgG₃, IgG₄, IgM, and IgA₁ were prepared and their abilities to stimulate histamine release from human peripheral blood leukocytes were investigated. As expected, anti-IgE caused 8% to 76% histamine release from the leukocytes of each of 14 nonallergic donors. In one subject anti-IgE alone had no effect, but a 15% histamine release did occur after the subsequent addition of a goat anti-mouse IgG antiserum to crosslink cell-bound anti-IgE molecules. Anti-IgG₄ alone caused 5% to 59% histamine release from the cells of four of 14 donors. Subsequent challenge with goat anti-mouse IgG caused an additional release of up to 15% of the basophil histamine, but only from leukocytes of donors responsive to anti-IgG₄ alone. No histamine release was detected after stimulation by monoclonal antibodies to IgG₁, IgG₂, IgG₃, IgM, or IgA₁. The results of this study indicate that monoclonal antibodies to IgG₄ as well as to IgE can stimulate human peripheral blood leukocytes to release histamine. These observations support the theory that antigen-IgG₄ interactions can stimulate histamine release from human basophils.