Characterization of a second secreted IgE isoform and identification of an asymmetric pathway of IgE assembly

被引:31
作者
Batista, FD [1 ]
Efremov, DG [1 ]
Burrone, OR [1 ]
机构
[1] INT CTR GENET ENGN & BIOTECHNOL,I-34012 TRIESTE,ITALY
关键词
epsilon heavy chains; carboxyl-terminal cysteine; IgE polymerization;
D O I
10.1073/pnas.93.8.3399
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A number of alternatively spliced epsilon transcripts have been detected in IgE-producing B cells, in addition to the mRNAs encoding the classical membrane and secreted IgE heavy (H) chains, In a recent study, we examined the protein products of three of these alternatively spliced isoforms and found that they are intracellularly retained and degraded because of their inability to assemble into complete IgE molecules, We have now similarly examined a more recently described epsilon mRNA species that is generated by splicing between a donor splice site immediately upstream of the stop codon in the ii-chain constant region exon 4 (CH4) and an acceptor site located in the 3' part of the second membrane exon, We show that this isoform is efficiently secreted by both plasma cells and B lymphocytes and therefore represents a second secreted IgE isoform (epsilon(S2)) The epsilon(S2) ii chain is only six amino acids longer than the classical secreted IgE H chain (epsilon(S1)) and contains a C-terminal cysteine, which is a characteristic sequence feature of mu and alpha H chains, However, unlike IgM and IgA, the epsilon(S2) C-terminal cysteine (Cys-554) does not induce polymerization of H(2)L(2) molecules (where L is light chain), but rather creates a disulfide bond between the two H chains that increases the rate of association into covalently bound H(2)L(2) monomers, This C-terminal cysteine also does not function as an intracellular retention element because the epsilon(S2) isoform was secreted in amounts equal to that of the epsilon(S1), both in B lymphocytes and in plasma cells, The epsilon(S2) Il chains secreted by B lymphocytes differed from the epsilon(S1) H chains in the extent of glycosylation, Interestingly, a difference in glycosylation between B-lymphocytes and plasma cells was also noted for both isoforms, The presence of the Cys-554 also allowed the identification of a distinctive asymmetric pathway of IgE assembly, common to both types of epsilon H chains.
引用
收藏
页码:3399 / 3404
页数:6
相关论文
共 29 条
[1]  
BATISTA FD, 1995, J IMMUNOL, V154, P209
[2]   Characterization of the human immunoglobulin epsilon mRNAs and their polyadenylation sites [J].
Batista, FD ;
Efremov, DG ;
Tkach, T ;
Burrone, OR .
NUCLEIC ACIDS RESEARCH, 1995, 23 (23) :4805-4811
[3]  
BROWN LS, 1989, J IMMUNOL, V142, P2070
[4]   STRUCTURE OF GENES FOR MEMBRANE AND SECRETED MURINE IGD HEAVY-CHAINS [J].
CHENG, HL ;
BLATTNER, FR ;
FITZMAURICE, L ;
MUSHINSKI, JF ;
TUCKER, PW .
NATURE, 1982, 296 (5856) :410-415
[5]  
DIAZSANCHEZ D, 1995, J IMMUNOL, V155, P1930
[6]   DIESEL EXHAUST PARTICLES INDUCE LOCAL IGE PRODUCTION IN-VIVO AND ALTER THE PATTERN OF IGE MESSENGER-RNA ISOFORMS [J].
DIAZSANCHEZ, D ;
DOTSON, AR ;
TAKENAKA, H ;
SAXON, A .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (04) :1417-1425
[7]   AN IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION GENE IS GENERATED FROM 3 SEGMENTS OF DNA - VH, D AND JH [J].
EARLY, P ;
HUANG, H ;
DAVIS, M ;
CALAME, K ;
HOOD, L .
CELL, 1980, 19 (04) :981-992
[8]   QUALITY-CONTROL OF ER SYNTHESIZED PROTEINS - AN EXPOSED THIOL-GROUP AS A 3-WAY SWITCH MEDIATING ASSEMBLY, RETENTION AND DEGRADATION [J].
FRA, AM ;
FAGIOLI, C ;
FINAZZI, D ;
SITIA, R ;
ALBERINI, CM .
EMBO JOURNAL, 1993, 12 (12) :4755-4761
[9]   THE EFFICIENCY OF CYSTEINE-MEDIATED INTRACELLULAR RETENTION DETERMINES THE DIFFERENTIAL FATE OF SECRETORY IGA AND IGM IN B-CELLS AND PLASMA-CELLS [J].
GUENZI, S ;
FRA, AM ;
SPARVOLI, A ;
BET, P ;
ROCCO, M ;
SITIA, R .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (10) :2477-2482