THE 2 MEMBRANE ISOFORMS OF HUMAN IGE ASSEMBLE INTO FUNCTIONALLY DISTINCT B-CELL ANTIGEN RECEPTORS

The human C epsilon gene expresses two membrane IgE heavy chain mRNAs which differ in the sequence that encodes their extracellular membrane -proximal domain. In the long IgE isoform (m(L)IgE), this domain conta ins a stretch of 52 amino acids which are absent in the short variant (m(S)IgE). We have now generated B cell transfectoma cell lines that e xpress these two isoforms and show that both types of mIgE form functi onal B cell antigen receptors (BCR). Both receptors associate with the Ig-alpha/Ig-beta heterodimer, as well as with protein kinases that ar e capable of phosphorylating this complex. Upon their cross-linking, b oth receptors can activate protein tyrosine kinases that phosphorylate the same substrate proteins. Both IgE receptors also associate with t wo novel proteins that do not bind to mIgM. Apart from these similarit ies, the two IgE-BCRs show several differences of which some are analo gous to the differences between the IgM- and IgD-BCRs. First, the m(S) IgE is transported to the cell surface at a higher rate than the m(L)I gE. Second, the two IgE-BCRs associate with differently glycosylated I g-alpha proteins, the m(L)IgE associates with the completely glycosyla ted form, whereas the m(S)IgE associates with an Ig-alpha glycoform th at is partially sensitive to endoglycosidase H. Third, the kinetics of protein tyrosine phosphorylation induced by receptor cross-linking is significantly different for the two IgE-BCRs. Finally, cross-linking of the m(S)IgE-BCR leads to growth inhibition of the B cell transfecto ma, whereas signaling through the m(L)IgE-BCR does not affect the cell ular proliferation. These data show that the two human membrane IgE is oforms assemble into functionally distinct antigen receptors which can induce different cellular responses.