权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of RAG expression in antibody-secreting B cell of SLE patients

SLE患者抗体分泌B细胞RAG表达分析

基本信息

批准号：
12470116
负责人：
SUZUKI Noboru
金额：
$ 9.09万
依托单位：
St. Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470116/
关键词：
SLE RAG anti-DNA antibody B lymphocytes Receptor editing apoptosis 抗DNA抗体 B細胞株 EBウイルス抗CD40抗体

项目摘要

We have investigated expression of recombination activating gene (RAG) proteins by peripheral blood mature B lymphocytes of normal subjects and patients with SLE. Although normal B cells did not express RAG proteins spontaneously, activated B cells expressed RAGs. Recombination signal sequence (RSS) binding activity of the RAGs was verified by a gel shift assay. Usage of a most downstream Jκ, Jκ5, was evident in activated B cells expressing RAGs. λ chain and intracellular RAGs were simultaneously expressed on the purified κ+ B cells after activation. Both findings suggest secondary light chain rearrangement in mature B cells. Some of RAG-expressing B cells could have failed in productive secondary rearrangement and they died via apoptosis. Thus, RAG-expressing B cells would revise their surface Ig or would die, leading to elimination of the autoreactive B cells.We found that anti-DNA autoAb secreting B cells in patients with SLE failed to express RAG spontaneously nor even with activation. Thus anti-DNA secreting B cells did not revise their Ig gene nor die via apoptosis, causing them to develop and persist autoAb secretion by SLE B cells. These results suggest that failure of RAG reexpression in anti-DNA secreting B cells may be important for autoAb production of SLE patients.

我们研究了正常人和SLE患者外周血成熟B淋巴细胞重组激活基因（RAG）蛋白的表达。虽然正常B细胞不自发表达RAG蛋白，但活化的B细胞表达RAG。通过凝胶位移测定验证RAG的结合信号序列（RSS）结合活性。在表达RAG的活化B细胞中，最下游的Jκ，Jκ5的使用是明显的。活化后的κ+ B细胞同时表达λ链和细胞内RAGs。这两个结果都表明成熟B细胞中存在二级轻链重排。一些表达RAG的B细胞可能在生产性二级重排中失败，并且它们通过凋亡而死亡。因此，表达RAG的B细胞会修改其表面IG或死亡，导致自身反应性B细胞的消除。我们发现，SLE患者中分泌抗DNA自身抗体的B细胞不能自发表达RAG，甚至不能活化。因此，分泌抗DNA的B细胞不会修改其IG基因，也不会通过细胞凋亡死亡，导致它们发展并持续SLE B细胞的自身抗体分泌。这些结果表明，RAG在分泌抗DNA的B细胞中重新表达的失败可能是SLE患者自身抗体产生的重要原因。