A bispecific antibody against human IgE and human FcγRII that inhibits antigen-induced histamine release by human mast cells and basophils
Article first published online: 4 JUN 2004
Volume 59, Issue 7, pages 772–780, July 2004
How to Cite
Tam, S. W., Demissie, S., Thomas, D. and Daëron, M. (2004), A bispecific antibody against human IgE and human FcγRII that inhibits antigen-induced histamine release by human mast cells and basophils. Allergy, 59: 772–780. doi: 10.1111/j.1398-9995.2004.00332.x
- Issue published online: 4 JUN 2004
- Article first published online: 4 JUN 2004
- Accepted for publication 23 June 2003
- mast cells;
- negative regulation;
- therapeutic antibody
Background: FcγRIIB are low-affinity immunoglobulin (Ig)G receptors that we previously demonstrated to negatively regulate IgE-induced mast cell activation when coaggregated with FcɛRI. Here, we engineered and characterized a bispecific reagent capable of coaggregating FcγRIIB with FcɛRI 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 FcγRII. This molecule was used to coaggregate FcɛRI with FcγRII 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 FcɛRI, with inhibitory receptors, such as FcγRIIB, that are constitutively expressed by mast cells and basophils.