Representation of rearranged VH gene segments in the human adult antibody repertoire.
Representation of rearranged VH gene segments in the human adult antibody repertoire.
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DOI：
10.4049/jimmunol.154.8.3902
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发表时间：
1995-04
影响因子：
4.4
通讯作者：
I. Suzuki;L. Pfister;A. Glas;C. Nottenburg;E. Milner
中科院分区：
文献类型：
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作者：
I. Suzuki;L. Pfister;A. Glas;C. Nottenburg;E. Milner
人成人抗体库的重链可变区组成定义不明确，但最近的证据表明，外周血B细胞可能表达VH基因的非随机分类。在本研究中，评估了单个VH基因区段对人Ab库的贡献。作为VH基因利用的量度，在两名成年受试者的外周血B细胞中评估重排中所含的八个单独的VH 3基因区段的出现频率。此外，在其中一名受试者中分析了含有9个单独VH 4基因片段的重排的发生频率。分析了2500多个独立的重排。对于对照，还进行了来自相同个体的未重排的VH 3和VH 4基因的扩增和随后的鉴定。该种系分析的结果表明，大约25个VH 3基因片段和9个VH 4基因片段可以定量扩增。然而，元素的使用并不均匀;一个VH 3元素V3-23和一个VH 4元素V4-34在重排中比它们各自家族的其他成员更频繁地出现。这种VH利用模式在8个月间隔后从同一受试者分离的B细胞中明显，表明库随时间的相对稳定性。这些结果表明，成人抗体库是由少数VH基因占主导地位，展示了一种模式的非随机利用，可能涉及优先重排和/或受体依赖性选择。
The heavy chain variable region composition of the human adult Ab repertoire is poorly defined, but recent evidence suggests that peripheral blood B cells may express a nonstochastic assortment of VH genes. In this study, the contribution of individual VH gene segments to the human Ab repertoire has been assessed. As a measure of VH gene utilization, the frequency of occurrence of eight individual VH3 gene segments contained in rearrangements was assessed in the peripheral blood B cells of two adult subjects. In addition, the frequency of occurrence of rearrangements containing nine individual VH4 gene segments was analyzed in one of the subjects. More than 2500 independent rearrangements were analyzed. For controls, amplifications and subsequent identification of nonrearranged VH3 and VH4 genes from the same individuals were also performed. The results of this germ-line analysis indicated that approximately 25 VH3 gene segments and nine VH4 gene segments could be amplified quantitatively. However, usage of elements was not uniform; one VH3 element, V3-23, and one VH4 element, V4-34, were represented among rearrangements more frequently than were other members of their respective families. This pattern of VH utilization was apparent in B cells isolated from the same subject after an 8-mo interval, indicating the relative stability of the repertoire over time. These results indicate that the adult human Ab repertoire is dominated by a few VH genes demonstrating a pattern of nonrandom utilization that could involve preferential rearrangement and/or receptor-dependent selection.