Receptor editing: an approach by autoreactive B cells to escape tolerance.
Receptor editing: an approach by autoreactive B cells to escape tolerance.
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DOI：
10.1084/jem.177.4.999
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发表时间：
1993-04-01
期刊：
影响因子：
--
通讯作者：
Weigert M
中科院分区：
文献类型：
--
作者：
Gay D;Saunders T;Camper S;Weigert M
为了确定携带抗DNA抗体的B细胞在正常小鼠中的命运，我们产生了携带良好表征的抗双链DNA抗体的重链（H）和轻链（L）基因的转基因小鼠。该抗体最初分离自患病的MRL/lpr小鼠，具有自发产生的抗DNA抗体的共同特征。结果表明，H/L转基因（tg）免疫球蛋白受体不表达的动物轴承两个tg，虽然单一tg动物（H或L）表达其转基因。年轻的H/L tg动物表达很少的B细胞，而成年H/L tg动物保持几乎正常的B细胞数量。成人B细胞所用的免疫球蛋白受体的分析表明，所有含有与内源性L链相关的tg H链。这些B细胞转录L tg以及重排的内源性L链基因，内源性L链基因转录的丧失导致3 H9 H/L tg产物的复活。这些细胞使用的内源性L链的检查表明，它们代表了V基因的高度限制的子集。总之，这些数据表明，自身反应性转基因B细胞可以重新排列内源性L链基因，改变表面受体。这些L链成功地与L tg竞争H链结合，并产生非自身反应性受体，使B细胞逃避缺失。我们认为这种受体编辑是未成熟的自身反应性B细胞逃避耐受的一种机制。
To determine the fate of anti-DNA antibody-bearing B cells in normal mice, we generated transgenic mice bearing the heavy (H) and light (L) chain genes of a well-characterized anti-double-stranded DNA antibody. This antibody was originally isolated from a diseased MRL/lpr mouse and has characteristics common to spontaneously arising anti-DNA antibodies. Results show that the H/L transgene (tg) immunoglobulin receptor is not expressed by animals bearing both tgs, although single tg animals (H or L) express their transgenes. Young H/L tg animals express few B cells, whereas adult H/L tg animals maintain almost normal B cell numbers. Analysis of the immunoglobulin receptors used by adult B cells shows that all contain the tg H chain in association with endogenous L chains. These B cells transcribe the L tg as well as the rearranged endogenous L chain gene, and loss of endogenous L chain gene transcription results in resurrection of the 3H9 H/L tg product. Examination of the endogenous L chains used by these cells shows that they represent a highly restricted subset of V genes. Taken together, these data suggest that autoreactive transgenic B cells can rearrange endogenous L chain genes to alter surface receptors. Those L chains that compete successfully with the L tg for H chain binding, and that create a nonautoreactive receptor, allow the B cell to escape deletion. We suggest that this receptor editing is a mechanism used by immature autoreactive B cells to escape tolerance.
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影响因子：
64.8
作者：
KLEINFIELD, R;HARDY, RR;WEIGERT, M
通讯作者：
WEIGERT, M
DOI：
10.1084/jem.173.2.409
发表时间：
1991-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Harada K;Yamagishi H
通讯作者：
Yamagishi H
DOI：
10.1073/pnas.77.4.2197
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
KOHLER, G
通讯作者：
KOHLER, G
影响因子：
64.8
作者：
ERIKSON, J;RADIC, MZ;WEIGERT, M
通讯作者：
WEIGERT, M
膜MU对免疫球蛋白基因重排的反馈抑制，而不是分泌的MU重链。
影响因子：
15.3
作者：
MANZ, J;DENIS, K;WITTE, O;BRINSTER, R;STORB, U
通讯作者：
STORB, U