The two membrane isoforms of human IgE assemble into functionally distinct B cell antigen receptors

被引:39
作者
Batista, FD
Anand, S
Presani, G
Efremov, DG
Burrone, OR
机构
[1] INT CTR GENET ENGN & BIOTECHNOL,AREA SCI PK,I-34012 TRIESTE,ITALY
[2] OSPED PEDIAT BURLO GAROFALO,I-34147 TRIESTE,ITALY
关键词
D O I
10.1084/jem.184.6.2197
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 contains 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 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 m(S)IgE is transported to the cell surface at a higher rate than the m(L)IgE. Second, the two IgE-BCRs associate with differently glycosylated Ig-alpha proteins, the m(L)IgE associates with the completely glycosylated form, whereas the m(S)IgE 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 m(S)IgE-BCR leads to growth inhibition of the B cell transfectoma, whereas signaling through the m(L)IgE-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.
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收藏
页码:2197 / 2205
页数:9
相关论文
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