Immobilization of the type I receptor for IgE initiates signal transduction in mast cells.
Clustering of the type I receptor for IgE (Fc(epsilon) RI) on mast cells initiates a cascade of biochemical processes that results in the secretion of inflammatory mediators. We have studied this clustering process in order to obtain information about receptor density and mobility required for initiating that cascade. Specifically, we examined the role of new cluster formation in sustaining the secretory response and the minimal cluster density required for initiating secretion. The experimental protocol adopted for these studies employed photoactivatable antigens and antigen-carrying solid surfaces which enabled us to control the density and mobility of the Fc epsilon RI within the cluster. Our results show that recruitment of new Fc(epsilon) RI into clusters, either by antigen exchange among Fc(epsilon) RI-bound IgE molecules or by IgE-bound Fc(epsilon) RI exchange with vacant receptors, is not required for sustaining the cellular secretory response. Furthermore, we find that the cell's secretory response is very sensitive to the density of immobilized Fc(epsilon) RIs, increasing steeply above a density of ca. 1000 immobilized molecules/microns 2. Taken together, these finding suggest that immobilization of a fraction of the randomly distributed Fc(epsilon) RIs that are in sufficient proximity on the surface of mucosal-type mast cells of the RBL-2H3 line initiates a degranulation signal, and that this is maintained as long as these receptors are kept within this distance. The above conclusions and the experimental protocol presented in this study are expected to have wider applications for the study and understanding of signaling by immuno (as well as other) receptors.
Tamir
I
I
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Schweitzer-Stenner
R
R
Pecht
I
I
D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000494:pharmacology*; D002460:Cell Line; D003429:Cross Reactions; D005456:Fluorescent Dyes; D006241:Haptens; D007073:Immunoglobulin E / Q000494:pharmacology* / Q000502:physiology; D008407:Mast Cells / Q000276:immunology*; D008433:Mathematics; D018448:Models, Immunological; D051381:Rats; D017455:Receptors, IgE / Q000502:physiology*; D012710:Serum Albumin, Bovine; D015398:Signal Transduction / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D005456:Fluorescent Dyes; D006241:Haptens; D017455:Receptors, IgE; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E