VH-gene representation in autoantibodies reflects the normal human B-cell repertoire.
VH-gene representation in autoantibodies reflects the normal human B-cell repertoire.
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自身抗体中的 VH 基因表现反映了正常的人类 B 细胞库。
DOI：
10.1111/j.1600-065x.1992.tb00834.x
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发表时间：
1992
影响因子：
8.7
通讯作者：
Schwartz,RS
中科院分区：
文献类型：
--
作者：
Stewart,AK;Huang,C;Long,AA;Stollar,BD;Schwartz,RS
在V-基因库的个别生殖系VH基因的复发，现在可以从胎儿，自身抗体和B细胞恶性肿瘤的限制性B细胞群体的正常成人的表达的V-基因库。为什么人B细胞优先利用这些单独的VH基因仍然是推测性的。然而，很明显，用于编码自身抗体的VH基因群体反映了正常表达的库（图7）。即便如此，抗DNA抗体中其他V基因如Dxp ′ 1的过度表达和自身免疫性疾病的致病性自身抗体中体细胞突变的存在继续表明对V基因选择的抗原性影响。我们假设，只有一小部分可用的生殖系V基因被利用在表达的剧目，和多特异性的天然存在的抗体和体细胞突变的CDR 3弥补了损失的多样性所带来的有限使用的潜在剧目。生殖系基因致病的机制尚不清楚，但可能与突变、调控丧失或环境因素有关（Isenberg et al. 1992）。那么，导致这些VH基因从正常控制中逃逸的机制是什么呢？什么抗原驱动（如果有的话）在SLE中产生抗DNA特异性？为什么真的是表达的剧目只使用一小部分可用的种系？为了回答这些问题，进一步研究的V-基因库的选定群体的抗原结合细胞和致病性IgG自身抗体是必要的，正在进行中。单个V基因对抗原结合和独特型的贡献也正在被剖析，并有望产生关于VH基因对自身免疫的相对贡献的重要信息。
The recurrence in the V-gene repertoire of individual germline VH genes can now be extended from the restricted B-cell populations of the fetus, autoantibodies and B-cell malignancies to the expressed V-gene repertoire of normal adults. Why the human B cell preferentially utilizes these individual VH genes remains speculative. However, it is apparent that the population of VH genes used to encode autoantibodies reflects the normal expressed repertoire (Fig. 7). Even so, the overrepresentation of other V genes such as Dxp'1 in anti-DNA antibodies and the presence of somatic mutation in the pathogenic autoantibodies of autoimmune disease continues to suggest an antigenic influence on V-gene selection. We postulate that only a fraction of available germline V genes are utilized in the expressed repertoire, and that polyspecificity of naturally occurring antibodies and somatic mutation of CDR3 compensate for the loss of diversity entailed by the limited use of the potential repertoire. The mechanisms by which germline genes become pathogenic remains unclear but they presumably relate to mutation, loss of regulatory control or perhaps environmental factors (Isenberg et al. 1992). What then are the mechanisms which lead to escape of these VH genes from normal control? What antigenic drive if any produces anti-DNA specificity in SLE? Why indeed is the expressed repertoire using only a fraction of the available germline? To answer these questions, further study of the V-gene repertoire of selected populations of antigen-binding cells and of pathogenic IgG autoantibodies is necessary and is ongoing. The contribution of individual V genes to antigen binding and idiotype is also being dissected and promises to yield important information about the relative contribution of VH genes to autoimmunity.