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A bispecific antibody against human IgE and human Fc γ RII that inhibits antigen‐induced histamine release by human mast cells and basophils
Author(s) -
Tam S. W.,
Demissie S.,
Thomas D.,
Daëron M.
Publication year - 2004
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2004.00332.x
Subject(s) - immunoglobulin e , histamine , antibody , receptor , mast cell , antigen , immunology , chemistry , fragment crystallizable region , basophil , microbiology and biotechnology , biology , biochemistry , pharmacology
Background: Fc γ RIIB are low‐affinity immunoglobulin (Ig)G receptors that we previously demonstrated to negatively regulate IgE‐induced mast cell activation when coaggregated with Fc ɛ RI. Here, we engineered and characterized a bispecific reagent capable of coaggregating Fc γ RIIB with Fc ɛ RI on human mast cells and basophils. Methods: A bispecific antibody was constructed by chemically crosslinking one Fab’ fragment against human IgE and one Fab’ fragment against human Fc γ RII. This molecule was used to coaggregate Fc ɛ RI with Fc γ RII on human mast cells and basophils sensitized with human IgE antibodies, and the effect of coaggregation was examined on mediator release upon challenge with specific antigen. Results: When used under these conditions, this bispecific antibody not only failed to trigger the release of histamine by IgE‐sensitized cells, but it also prevented specific antigen from triggering histamine release. Comparable inhibitions were observed with mast cells and basophils derived in vitro from cord blood cells and with peripheral blood basophils. Conclusions: The bispecific antibody described here is the prototype of similar molecules that could be used in new therapeutic approaches of allergic diseases based on the coaggregation of activating receptors, such as Fc ɛ RI, with inhibitory receptors, such as Fc γ RIIB, that are constitutively expressed by mast cells and basophils.