Mast cell stimulation by co-clustering the type I Fcε-receptors with mast cell function-associated antigens

Abstract

The secretory response of rat mucosal-type mast cells (line RBL 2H3) to stimuli produced by clustering or co-clustering two of its membranal components; the type I Fcε receptor and the mast cell function associated antigen (MAFA) was investigated. The primary reagents employed for this purpose were Fab fragments of the monoclonal antibodies J17 and G63 specific to the above respective proteins. The Fabs were then aggregated by F(ab′) 2 fragments of mouse IgG specific goat antibodies. This reaction was assumed to yield predominantly three different bivalent clustering reagents. Namely, dimers of the FcεRI specific (J17-Fab) 2; dimers of the MAFA specific, (G63-Fab) 2 and bispecific (J17-Fab-G63-Fab) dimers. The observed cellular secretory response was analyzed by employing a model which accounts for the clustering and co-clustering of FcεRIs and MAFAs by the above protocols. Results of this analysis provided evidence that at least some of the MAFA molecules are physically associated with the FcεRI. As a consequence, clustering of MAFA and FcεRI by bispecific J17-Fab-G63-Fab dimers induces secretion at comparatively low concentrations of these reagents, though with a significantly lower maximal response than that caused by the respective monospecific reagent (J17-Fab) 2. This result most likely reflects the inhibitory capacity of MAFA-FcεRI interaction.