Cellular responses elicited by cell-surface receptors differ depending on stimulus strength. In Science, Rivera and colleagues investigate how the high-affinity IgE receptor (FcεRI) distinguishes high- and low-affinity stimulation to modulate mast cell responses. At antigen concentrations that induce similar receptor phosphorylation, 2NP, a low-affinity antigen, elicits less degranulation and cytokine production, but enhanced chemokine production, as compared to DNP, a high-affinity antigen for the FcεRI-bound DNP-specific IgE. Compared to DNP, 2NP induces more diffuse, less organized FcεRI clusters, resulting in changes in the balance of receptor-associated kinases, namely increased co-localization of the Src family kinase Fgr and increased phosphorylation of the adaptor LAT2 relative to LAT1. Fgr and LAT2 enhance CCL2 chemokine responses at the expense of mast cell degranulation. In vivo, 2NP stimulation results in increased recruitment of monocytes and macrophages compared to a DNP response, which recruits more neutrophils, suggesting discrimination of antigen-antibody affinity by the FcεRI receptor results in distinct physiological outcomes.

Science (6 February 2014) doi:10.1126/science.1246976