title: Functional Fc epsilonRI engagement by a second secretory IgE isoform detected in humans.
abstract: We have recently reported that besides the most abundant form epsilonS1, there exists another human secretory epsilon H chain isoform, epsilonS2, resulting from alternative splicing in the epsilonCH4 exon. Using a specific antibody targeted to the epsilonS2-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 epsilonS2 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 Fc epsilonRI, 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 epsilonS2 tailpiece can exert an effect on the interaction with the alpha chain of Fc epsilonRI.
authors: International Centre for Genetic Engineering and Biotechnology, Area Science Park, Trieste, Italy. r.lorenzi@ich.ucl.ac.uk
authors: R
authors: R
authors: Lorenzi
authors: M H
authors: MH
authors: Jouvin
authors: O R
authors: OR
authors: Burrone
mesh_terms: D006801:Humans; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D014066:Palatine Tonsil / Q000276:immunology / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger; D017455:Receptors, IgE / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E