A lipopolysaccharide-induced DNA-binding protein for a class II gene in B cells is distinct from NF-kappa B.
A lipopolysaccharide-induced DNA-binding protein for a class II gene in B cells is distinct from NF-kappa B.
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B 细胞中 II 类基因的脂多糖诱导的 DNA 结合蛋白与 NF-kappa B 不同。
DOI：
10.1128/mcb.9.8.3184-3192.1989
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发表时间：
1989
影响因子：
5.3
通讯作者：
Glimcher,LH
中科院分区：
文献类型：
--
作者：
Gravallese,EM;Boothby,MR;Smas,CM;Glimcher,LH
II类（Ia）主要组织相容性复合体分子是细胞表面蛋白，通常由免疫系统的有限细胞亚群表达。这些分子调节T细胞的活化，是抗原呈递和免疫反应启动所必需的。Ia在B细胞中的表达既受B细胞发育阶段的影响，也受外界刺激的影响。先前已经证明，用脂多糖（LPS）处理B细胞导致Ia蛋白表面表达增加。然而，我们已经证实，LPS处理导致编码Ia蛋白的mRNA显著减少，并持续至少18小时。在a αk的上游调控区域，存在NF-κ b样结合位点。我们已经从脾脏主要由B细胞组成的胸腺小鼠的提取物中鉴定出一种lps诱导的dna结合蛋白。结合活性在未受刺激的脾细胞中呈低水平存在，并通过LPS处理而增加。该蛋白结合la a αkgene调控区域的两个位点，其中一个含有NF-κ b样结合位点。含有这些位点的DNA片段相互竞争以结合蛋白质。通过DNase I足迹分析鉴定出一个目标结合序列，命名为lps响应元件。尽管该靶序列包含NF-κB样结合位点，但与突变寡核苷酸的竞争表明，对NF-κB结合至关重要的碱基并不需要与lps诱导蛋白结合。因此，我们假设这种诱导蛋白代表了一种不同于NF-κB的LPS作用的新介质，并且可能是解释编码Ia蛋白的mRNA减少的一种机制。
Class II (Ia) major histocompatibility complex molecules are cell surface proteins normally expressed by a limited subset of cells of the immune system. These molecules regulate the activation of T cells and are required for the presentation of antigens and the initiation of immune responses. The expression of Ia in B cells is determined by both the developmental stage of the B cell and by certain external stimuli. It has been demonstrated previously that treatment of B cells with lipopolysaccharide (LPS) results in increased surface expression of Ia protein. However, we have confirmed that LPS treatment results in a significant decrease in mRNA encoding the Ia proteins which persists for at least 18 h. Within the upstream regulatory region of Aαk, an NF-κB-Iike binding site is present. We have identified an LPS-induced DNA-binding protein in extracts from athymic mice whose spleens consist predominantly of B cells. Binding activity is present in low levels in unstimulated spleen cells and is increased by LPS treatment. This protein binds to two sites in a regulatory region of the la Aαkgene, one of which contains the NF-κB-like binding site. DNA fragments containing these sites cross-compete for protein binding. Analysis by DNase I footprinting identified a target binding sequence, named the LPS-responsive element. Although this target sequence contains an NF-κB-like binding site, competition with a mutant oligonucleotide demonstrated that bases critical for NF-κB binding are not required for binding of the LPS-inducible protein. Therefore, we hypothesize that this inducible protein represents a new mediator of LPS action, distinct from NF-κB, and may be one mechanism to account for the decrease in mRNA encoding the Ia proteins.