Shedded type I and type II transmembrane molecules
CD40 and CD5 (Figure 3, a, b) were elevated through low affinity IgE after 6 and 24 hours. CD40, CD5, SLAMF4, IL10RB, CD6 and TGF-a were differentially regulated with low- and high affinity IgE. PD-L1 was upregulated by both low- and high affinity IgE (Figure 3, g).
The soluble TMII molecules TNFSF12 and TNFSF14 (Figure 3, j, k) were upregulated primarily through activation with high affinity IgE at all time points, while low level upregulation by low affinity IgE activation happened later.
Discussion
We hereby confirm that increase of IgE affinity increases both reactivity and sensitivity of degranulation measured as CD63 activation, and de novo synthesis of lipid mediators measured as the release of PGD2 and its metabolites by human mast cells (Figure 1). Furthermore, we confirm results obtained in murine models, that IgE affinity directs the soluble mediator expression from activated mast cells(2) which may dictate the late phase response in vivo. Activation of human mast cells through high affinity IgE induced secretion of cytokines and chemokines, whereas stimulation through low affinity IgE resulted primarily in the release of membrane bound receptors.