The two 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 (mLIgE), this domain contains a stretch of 52 amino acids which are absent in the short variant (mSIgE). We have now generated B cell transfectoma cell lines that express these two isoforms and show that both types of mIgE form functional B cell antigen receptors (BCR). Both receptors associate with the Ig-alpha/Ig-beta heterodimer, as well as with protein kinases that are capable of phosphorylating this complex. Upon their cross-linking, both receptors can activate protein tyrosine kinases that phosphorylate the same substrate proteins. Both IgE receptors also associate with two novel proteins that do not bind to mIgM. Apart from these similarities, the two IgE-BCRs show several differences of which some are analogous to the differences between the IgM- and IgD-BCRs. First, the mSIgE is transported to the cell surface at a higher rate than the mLIgE. Second, the two IgE-BCRs associate with differently glycosylated Ig-alpha proteins, the mLIgE associates with the completely glycosylated form, whereas the mSIgE associates with an Ig-alpha glycoform that 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 mSIgE-BCR leads to growth inhibition of the B cell transfectoma, whereas signaling through the mLIgE-BCR does not affect the cellular proliferation. These data show that the two human membrane IgE isoforms assemble into functionally distinct antigen receptors which can induce different cellular responses.
Batista
F D
FD
International Center for Genetic Engineering and Biotechnology, Trieste, Italy.
Anand
S
S
Presani
G
G
Efremov
D G
DG
Burrone
O R
OR
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D005434:Flow Cytometry; D005803:Genes, Immunoglobulin; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D014158:Transcription, Genetic; D014162:Transfection
D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D007073:Immunoglobulin E