Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors

Abstract

Allergic symptoms result from the release of granular and lipidic mediators and of cytokines by inflammatory cells. The whole process is initiated by the aggregation of mast cell and basophil high-affinity IgE receptors (FcεRI) by IgE and antigen. We report here that IgE-induced release of mediator and cytokine can be inhibited by cross-linking FcεRI to low-affinity IgG receptors (FcγRII) which are constitutively expressed on mast cells and basophils. Using a model of stable transfectants in RBL-2H3 cells expressing endogeneous rat FcεRI and recombinant marine FcγRII, we showed that inhibition requires that FcεRI be cross-linked to FcγRII by the same multivalent ligand. Inhibition of cross-linked receptors left non- cross-linked FcεRI capable of triggering mediator release and was reversible upon disengagement. Both isoforms of wild-type FcγRII were equally capable of inhibiting FcεRI-mediated mast cell activation provided they had an intact intracytoplasmic domain. Our results demonstrate that mast cell secretory responses triggered by high-affinity receptors for IgE may be controlled by low-affinity receptors for IgG. This regulation of FcεRI- mediated mast cell activation is of potential interest in mast cell physiology and in allergic pathology.