Immunoglobulin beta signaling regulates locus accessibility for ordered immunoglobulin gene rearrangements.
Immunoglobulin beta signaling regulates locus accessibility for ordered immunoglobulin gene rearrangements.
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DOI：
10.1084/jem.191.8.1333
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发表时间：
2000-04-17
期刊：
影响因子：
--
通讯作者：
Karasuyama H
中科院分区：
文献类型：
--
作者：
Maki K;Nagata K;Kitamura F;Takemori T;Karasuyama H
抗原受体基因重排在一个给定的基因座是严格调控的细胞谱系和发育阶段的一个不明确的机制。为研究前体B细胞抗原受体（pre-BCR）信号在B细胞分化过程中免疫球蛋白（IG）基因重排调控中的可能作用，采用新开发的μ重（H）链膜外显子（μm）缺陷小鼠系统。在该系统中，抗体介导的IGβ在发育停滞的祖B（pro-B）细胞上的交联模拟前BCR信号传导，以诱导体内早期B细胞分化。连接介导的聚合酶链反应分析显示，IGβ交联诱导了IG基因重排的重定向，即抑制了H链位点的正在进行的重排，并激活了轻链（L）位点的重排。交联后，发现κL链生殖系转录上调，而VH生殖系转录迅速下调。值得注意的是，在H和L链基因座的可及性的这种改变甚至在细胞分化的诱导变得可通过表面表型的变化检测到之前就被检测到。因此，通过IGβ的前BCR信号传导似乎通过改变IG位点的可接近性来调节有序的IG基因重排。
The antigen receptor gene rearrangement at a given locus is tightly regulated with respect to cell lineage and developmental stage by an ill-defined mechanism. To study the possible role of precursor B cell antigen receptor (pre-BCR) signaling in the regulation of the ordered immunoglobulin (Ig) gene rearrangement during B cell differentiation, a newly developed system using μ heavy (H) chain membrane exon (μm)-deficient mice was employed. In this system, the antibody-mediated cross-linking of Igβ on developmentally arrested progenitor B (pro-B) cells mimicked pre-BCR signaling to induce early B cell differentiation in vivo. Analyses with ligation-mediated polymerase chain reaction revealed that the Igβ cross-linking induced the redirection of Ig gene rearrangements, namely, the suppression of ongoing rearrangements at the H chain locus and the activation of rearrangements at the light (L) chain locus. Upon the cross-linking, the κL chain germline transcription was found to be upregulated whereas the VH germline transcription was promptly downregulated. Notably, this alteration of the accessibility at the H and L chain loci was detected even before the induction of cellular differentiation became detectable by the change of surface phenotype. Thus, the pre-BCR signaling through Igβ appears to regulate the ordered Ig gene rearrangement by altering the Ig locus accessibility.
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DOI：
10.1084/jem.185.4.609
发表时间：
1997-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Constantinescu A;Schlissel MS
通讯作者：
Schlissel MS
影响因子：
4.4
作者：
CHEN, JZ;TROUNSTINE, M;HUSZAR, D
通讯作者：
HUSZAR, D
DOI：
10.1084/jem.184.6.2423
发表时间：
1996-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Maki K;Sunaga S;Ikuta K
通讯作者：
Ikuta K
影响因子：
64.5
作者：
LASSOUED, K;NUNEZ, CA;COOPER, MD
通讯作者：
COOPER, MD
影响因子：
64.5
作者：
KARASUYAMA, H;ROLINK, A;MELCHERS, F
通讯作者：
MELCHERS, F