title: Presence of IgG4 on the membrane of human basophils. Histamine release is induced by monoclonal antibodies directed against the Fab but not the Fc region of the IgG4 molecule.
abstract: We have studied the possible role of human IgG4 as an anaphylactic antibody. For that purpose, we have determined the induction of histamine release (HR) from human basophils by anti-IgE and anti-IgG4 monoclonal antibodies (MoAbs) recognizing different epitopes located at the Fc and Fab regions of the IgG4 molecule. The results show that anti-IgG4 (Fab) MoAb was able to induce HR in 93% of donors tested, with no differences between atopics and non-atopics. That HR is calcium dependent and is accompanied by the synthesis and release of leukotriene C4. In contrast, no HR could be induced by anti-IgG4(Fc) MoAbs in any individual, even in the presence of D2O or after a second challenge with a polyclonal goat anti-mouse IgG antibody. The results obtained suggest the presence of IgG4 on the basophil membrane and that the epitope recognized by the anti-IgG4 (Fc) MoAbs is probably hidden in cell-bound IgG4. This was demonstrated by immunofluorescence techniques: IgG4 bound to the basophil membrane could be detected with anti-IgG4(Fab) but not with anti-IgG4(Fc) MoAbs. In addition, we found that nine donors were unresponsive to an anti-IgE stimulus, while they released histamine efficiently after challenge with anti-IgG4(Fab), suggesting the existence of different receptors for both immunoglobulins.
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001491:Basophils / Q000378:metabolism*; D003903:Deuterium / Q000494:pharmacology; D017666:Deuterium Oxide; D004492:Edetic Acid / Q000494:pharmacology; D019793:Fluorescein; D005452:Fluoresceins; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D012016:Reference Values; D014867:Water / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D005452:Fluoresceins; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D014867:Water; D007073:Immunoglobulin E; D004492:Edetic Acid; D003903:Deuterium; D017666:Deuterium Oxide; D019793:Fluorescein