Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum.
Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum.
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DOI：
10.1186/1471-2172-13-72
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发表时间：
2012-12-26
期刊：
影响因子：
3
通讯作者：
Tsubata T
中科院分区：
文献类型：
--
作者：
Hitomi Y;Adachi T;Tsuchiya N;Honda Z;Tokunaga K;Tsubata T
CD 72是在B细胞上表达的抑制性共受体。我们先前证明了在携带SLE易感FCGR 2B基因型（FCGR 2B-232 Thr/Thr）的个体中，CD 72基因多态性与人类系统性红斑狼疮（SLE）易感性显著相关。人CD 72基因座产生缺少外显子8（CD 72 Δ ex 8）和全长CD 72（CD 72 fl）的剪接同种型，CD 72多态性调节外显子8跳跃。在此，我们证明了携带疾病保护性CD 72基因型的个体比携带其他CD 72基因型的个体表现出显著较低的血清免疫球蛋白水平（P < 0.05）。尽管外周血B细胞中CD 72 fl的表达水平与CD 72基因型无关，但在携带疾病保护性CD 72基因型的个体中，CD 72 Δ ex 8的蛋白水平升高，表明CD 72 Δ ex 8在调节抗体产生中起关键作用。通过在小鼠细胞系中表达这些人CD 72同种型，我们进一步证明了CD 72 Δ ex 8在内质网（ER）中积累并且不能调节BCR信号传导，而人CD 72 fl被有效转运至细胞表面并且抑制通过B细胞抗原受体（BCR）的信号传导，如小鼠CD 72的情况。人类CD 72多态性似乎通过调节ER定位的CD 72 Δ ex 8的表达来调节抗体产生以及对SLE的易感性。
CD72 is an inhibitory co-receptor expressed on B cells. We previously demonstrated significant association of the polymorphism of the CD72 gene with susceptibility to human systemic lupus erythematosus (SLE) in individuals carrying a SLE-susceptible FCGR2B genotype (FCGR2B-232Thr/Thr). The human CD72 locus generates a splicing isoform that lacks exon 8 (CD72Δex8) as well as full-length CD72 (CD72fl), and the CD72 polymorphism regulates exon 8 skipping. Here we demonstrated that individuals carrying the disease-protective CD72 genotype exhibit significantly lower serum immunoglobulin levels than do individuals carrying other CD72 genotypes (P < 0.05). Although expression level of CD72fl in the peripheral blood B cells was similar regardless of CD72 genotype, the protein level of CD72Δex8 was increased in individuals carrying the disease-protective CD72 genotype, suggesting a crucial role of CD72Δex8 in regulation of antibody production. By expressing these human CD72 isoforms in mouse cell lines, we further demonstrated that CD72Δex8 is accumulated in endoplasmic reticulum (ER) and fails to regulate BCR signaling whereas human CD72fl is efficiently transported to the cell surface and inhibits signaling through the B cell antigen receptor (BCR), as is the case for mouse CD72. Human CD72 polymorphism appears to regulate antibody production as well as susceptibility to SLE by regulating expression of ER-localizing CD72Δex8.
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DOI：
10.1016/j.bbrc.2007.10.137
发表时间：
2008-01-04
影响因子：
3.1
作者：
Yan, Bin-Cheng;Adachi, Takahiro;Tsubata, Takeshi
通讯作者：
Tsubata, Takeshi
DOI：
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发表时间：
1997-11-03
期刊：
The Journal of experimental medicine
影响因子：
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DOI：
10.1038/nrrheum.2010.176
发表时间：
2010-12
期刊：
Nature reviews. Rheumatology
影响因子：
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作者：
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影响因子：
30.5
作者：
Fukuyama, H;Nimmerjahn, F;Ravetch, JV
通讯作者：
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DOI：
10.1073/pnas.86.4.1352
发表时间：
1989-02-01
影响因子：
11.1
作者：
NAKAYAMA, E;VONHOEGEN, I;PARNES, JR
通讯作者：
PARNES, JR