BLyS and B cell autoimmunity.
BLyS and B cell autoimmunity.
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BLyS 和 B 细胞自身免疫。
DOI：
10.1159/000066854
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Kimberly,Robert
中科院分区：
文献类型：
--
作者：
Zhou,Tong;Zhang,Jun;Carter,Robert;Kimberly,Robert
BLySTM蛋白是一种重要的B细胞生存因子，其受体是最近发现的肿瘤坏死因子配体和受体超家族成员[1]。这个超家族的成员密切参与免疫细胞的增殖和死亡的调节，因此对自身免疫性疾病的发病机制的特征特别感兴趣(表1)。众所周知，这个超家族中的几个经典成员，如肿瘤坏死因子-α和其他淋巴毒素及其受体，在自身免疫性疾病中发挥着重要作用。这些因素不仅介导了自身免疫性疾病的病理效应，而且还改变了免疫反应，从而导致自身免疫反应的潜在耐受性丧失和放大。Fas和Fas配体是该家族中具有诱导凋亡能力的成员，参与了T细胞的活化诱导死亡。在小鼠中发现Fas或Fas配体基因的突变导致自发的自身免疫性狼疮样疾病，其特征是自身抗体的产生和淋巴结病，这与T和B细胞耐受性的丧失有关。最近，已经确定了激活诱导细胞死亡的其他途径，包括死亡受体DR4和DR5，以及肿瘤坏死因子相关的凋亡诱导配体TRAIL，它们可能在自身免疫性疾病中发挥抑制作用[3]。TRAIL对自身免疫易感小鼠淋巴病变的发生和抗dsDNA抗体的产生均有抑制作用，提示TRAIL可有效地抑制自身免疫反应。观察)。最近发现的另外两个死亡受体DR3和DR6可能参与调节T细胞反应，从而扩大了操纵细胞凋亡的机会[4，5]。除了成对的死亡受体-配体系统外，
BLySTM protein, a crucial B cell survival factor, and its receptors are recently identified members of the TNF ligand and receptor superfamily [1]. The members of this superfamily are intimately involved in the regulation of the proliferation and death of immune cells and are therefore of particular interest in the characterization of the pathogenesis of autoimmune disease (table 1). It is well established that several classic members of this superfamily, such as TNF-α and other lymphotoxins and their receptors, play important roles in autoimmune diseases. These factors act not only to mediate the pathologic effects of autoimmune diseases, but also to modify the immune response, thereby contributing to the underlying loss of tolerance and amplification of the autoimmune response. Fas and Fas ligand, members of this family with apoptosis-inducing capability, are involved in the activation-induced death of T cells. The finding that mutations of the fas or fas ligand genes in mice cause spontaneous autoimmune lupus-like diseases, characterized by autoantibody production and lymphoadenopathy, has implicated defective apoptosis in the loss of T and B cell tolerance [2]. More recently, alternative pathways for activation-induced cell death have been identified, including the death receptors, DR4 and DR5, and the TNF-related apoptosisinducing ligand, TRAIL, which may play an inhibitory role in autoimmune disease [3]. The inhibition of the development of lymphadenopathy and the production of anti-dsDNA antibody on the treatment of autoimmune-prone mice with TRAIL suggests that TRAIL might be used effectively to inhibit autoimmune response (unpubl. observation). The opportunities for manipulation of apoptosis have been expanded by the recent identification of two other death receptors, DR3 and DR6, which are likely to be involved in the regulation of T cell response [4, 5]. In addition to the paired death receptor-ligand systems,