Functional FcεRI engagement by a second secretory IgE isoform detected in humans

Abstract

We have recently reported that besides the most abundant form ϵS1, there exists another human secretory ϵ H chain isoform, ϵS2, resulting from alternative splicing in the ϵCH4 exon. Using a specific antibody targeted to the ϵS2-specific C-terminal tailpiece, we now show that this second secretory IgE isoform (IgE-S2) is constitutively co-expressed with the classical secretory IgE-S1 by human myeloma cells. The ϵS2 variant was also detected in tonsils and in the serum of three non-atopic donors, but was absent in the vast majority of sera of both atopic and non-atopic individuals tested, indicating rare serum expression. IgE-S2 is capable of binding to cells expressing FcϵRI, the high-affinity receptor for IgE. Analysis of intracellular tyrosine phosphorylation signal, degranulation, and rate of receptor internalization suggest a quantitatively lower response by IgE-S2 compared to IgE-S1. The modest differences observed do not appear to overall affect the degranulation competency of IgE-S2, but suggest that the unique structure of the ϵS2 tailpiece can exert an effect on the interaction with the α chain of FcϵRI.