The transcription factor early growth response 1 (Egr-1) advances differentiation of pre-B and immature B cells.
The transcription factor early growth response 1 (Egr-1) advances differentiation of pre-B and immature B cells.
复制标题
转录因子早期生长响应1（EGR-1）的进步pre-B和未成熟B细胞的分化。
DOI：
10.1084/jem.188.12.2215
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发表时间：
1998-12-21
期刊：
影响因子：
--
通讯作者：
Eibel H
中科院分区：
文献类型：
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作者：
Dinkel A;Warnatz K;Ledermann B;Rolink A;Zipfel PF;Bürki K;Eibel H
在成熟的B淋巴细胞中，锌指转录因子早期生长反应1（Egr-1）是在B细胞抗原受体结合后诱导的许多立即早期基因之一。然而，其在淋巴细胞生成早期阶段的作用仍不清楚。通过检测骨髓B细胞亚群，我们发现在原/前B和未成熟B淋巴细胞中存在Egr-1转录物，在白细胞介素（IL）-7存在下在基质细胞上培养的原/前B-I细胞中存在Egr-1蛋白。在重组酶激活基因（RAG）-2缺陷小鼠中，B淋巴细胞谱系中Egr-1转基因过表达，pro/pre-B-I细胞可分化通过B220低BP-1−阶段的发育阻滞，进入B220低BP-1+ pre-B-I细胞阶段，但不能进一步分化至B220低BP-1+ CD 25 + pre-B-II细胞阶段。因此，在早期B淋巴细胞生成过程中，从B220低BP-1− IL-2 R − pro/pre-B-I阶段到B220低BP-1+ IL-2 R + pre-B-II阶段的进展似乎至少发生在两个不同的步骤中，第一步到B220低BP-1+ pre-B-I阶段的细胞可以通过Egr-1单独过表达来促进。表达Egr-1转基因的野生型小鼠骨髓B细胞中成熟免疫球蛋白（IG）M+ B220高的比例增加，未成熟IgM+ B220低的比例减少。由于转基因和对照前体B细胞显示相当的增殖模式，Egr-1的过表达似乎也促进进入成熟B细胞阶段。对潜在Egr-1靶基因表达模式变化的分析显示，Egr-1增强前B和未成熟B细胞中氨肽酶BP-1/6C 3的表达，并上调IgM+ B细胞中孤儿核受体nur 77的表达。
In mature B lymphocytes, the zinc finger transcription factor early growth response 1 (Egr-1) is one of the many immediate-early genes induced upon B cell antigen receptor engagement. However, its role during earlier stages of lymphopoiesis has remained unclear. By examining bone marrow B cell subsets, we found Egr-1 transcripts in pro/pre-B and immature B lymphocytes, and Egr-1 protein in pro/pre-B–I cells cultivated on stroma cells in the presence of interleukin (IL)-7. In recombinase-activating gene (RAG)-2–deficient mice overexpressing an Egr-1 transgene in the B lymphocyte lineage, pro/pre-B–I cells could differentiate past a developmental block at the B220low BP-1− stage to the stage of B220low BP-1+ pre-B–I cells, but not further to the B220low BP-1+ CD25+ stage of pre-B–II cells. Therefore, during early B lymphopoiesis progression from the B220low BP-1− IL-2R− pro/pre-B–I stage to the B220low BP-1+ IL-2R+ pre-B–II stage seems to occur in at least two distinct steps, and the first step to the stage of B220low BP-1+ pre-B–I cells can be promoted by the overexpression of Egr-1 alone. Wild-type mice expressing an Egr-1 transgene had increased proportions of mature immunoglobulin (Ig)M+ B220high and decreased proportions of immature IgM+ B220low bone marrow B cells. Since transgenic and control precursor B cells show comparable proliferation patterns, overexpression of Egr-1 seems also to promote entry into the mature B cell stage. Analysis of changes in the expression pattern of potential Egr-1 target genes revealed that Egr-1 enhances the expression of the aminopeptidase BP-1/6C3 in pre-B and immature B cells and upregulates expression of the orphan nuclear receptor nur77 in IgM+ B cells.