Basophil signalling in IgE-mediated basophil degranulation
Crosslinking of IgE presented on FcεRI, the high affinity IgE receptor on blood basophils, results in increased phosphorylation of ITAMs of the FcεRI𝛽𝛾 subunits, and of the SH2-domains of kinases Syk and Lyn12, which are under constant counter-regulation by dephosphorylation through CD4513. Net phosphorylation of FceRI𝛽𝛾 and Syk leads to massive amplification of the initial signal, similar to that of neuronal signalling, and regulated exocytosis of secretory lysosomes that stain with basic dyes as they contain histamine, histidine decarboxylase, heparin and proteases14. Immune-regulated exocytosis uses SNAP23 and VAMP8 whereas SNAP25 and VAMP1 and VAMP2 are used in neuronal signalling15. Degranulation has been studied mainly in murine mast cells and the RBL cell line, as these can be cultured in sufficient quantities16. IgE-mediated activation is an example of a bi- or multivalent activation mechanism through adaptive immune signalling. Use of wortmannin sensitive kinases PI3K and MAPK can confirm the IgE-mediated origin of the activating signal1,17, since wortmannin can thus inhibit the IgE pathway. The fusion of secretory lysosomes with the cell membrane in basophil and mast cells may also be activated through G-coupled protein receptors linked to receptors for univalent exogenous substances like fMLP and ligands for MRGPRX218, and may be modulated by receptors for endogenous univalent substances like PAF, IL8 and C5a14.