CD45 exclusion- and cross-linking-based receptor signaling together broaden FcεRI reactivity

Sci Signal. 2018 Dec 18;11(561):eaat0756. doi: 10.1126/scisignal.aat0756.


For many years, the high-affinity receptor for immunoglobulin E (IgE) FcεRI, which is expressed by mast cells and basophils, has been widely held to be the exemplar of cross-linking (that is, aggregation dependent) signaling receptors. We found, however, that FcεRI signaling could occur in the presence or absence of receptor cross-linking. Using both cell and cell-free systems, we showed that FcεRI signaling was stimulated by surface-associated monovalent ligands through the passive, size-dependent exclusion of the receptor-type tyrosine phosphatase CD45 from plasma membrane regions of FcεRI-ligand engagement. Similarly to the T cell receptor, FcεRI signaling could also be initiated in a ligand-independent manner. These data suggest that a simple mechanism of CD45 exclusion-based receptor triggering could function together with cross-linking-based FcεRI signaling, broadening mast cell and basophil reactivity by enabling these cells to respond to both multivalent and surface-presented monovalent antigens. These findings also strengthen the case that a size-dependent, phosphatase exclusion-based receptor triggering mechanism might serve generally to facilitate signaling by noncatalytic immune receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRISPR-Cas Systems
  • Cell Degranulation*
  • Cross-Linking Reagents / chemistry
  • Immunoglobulin E / metabolism*
  • Integrins / metabolism
  • Leukemia, Basophilic, Acute / immunology*
  • Leukemia, Basophilic, Acute / metabolism
  • Leukemia, Basophilic, Acute / pathology
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism*
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Rats
  • Receptors, IgE / antagonists & inhibitors
  • Receptors, IgE / genetics
  • Receptors, IgE / metabolism*
  • Tumor Cells, Cultured


  • Cross-Linking Reagents
  • FCER1A protein, rat
  • Integrins
  • Receptors, IgE
  • Immunoglobulin E
  • Leukocyte Common Antigens
  • Ptprc protein, rat