Weng N P, Snyder J G, Yu-Lee L Y, Marcus D M
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.
Eur J Immunol. 1992 Apr;22(4):1075-82. doi: 10.1002/eji.1830220430.
The human immunoglobulin VH4 gene family is thought to contain approximately 10 germ-line genes and to exhibit little polymorphism. We report here an analysis of VH4 germ-line genes that were amplified from DNA of two unrelated individuals. Ten unique (non-repetitive) sequences were obtained from individual A and 11 from individual B. Nine of these sequences represent new germ-line genes, and 8/9 exhibit only 89%-96% similarity to genes identified previously. Subsets of VH4 genes displayed distinctive nucleotide motifs that account for most of the differences between them. This observation suggests that diversity in the VH4 gene family arose from the acquisition of blocks of nucleotides, rather than by accumulation of point mutations. These nucleotide blocks could have been acquired by gene conversion or by homologous recombination. All of the VH4 genes have a potential N-linked glycosylation site at Asn 60, and some genes encode a second site at Asn 52. The VH4 gene family is larger and more polymorphic than appreciated previously. Immunoglobulin gene polymorphism may make a significant contribution to hereditary variations in the immune response and to the genetic predisposition to autoimmune diseases.
人类免疫球蛋白VH4基因家族被认为包含大约10个种系基因，且多态性较低。我们在此报告对从两名无关个体的DNA中扩增出的VH4种系基因的分析。从个体A获得了10个独特（非重复）序列，从个体B获得了11个。这些序列中的9个代表新的种系基因，其中8/9与先前鉴定的基因仅表现出89%-96%的相似性。VH4基因亚组显示出独特的核苷酸基序，这解释了它们之间的大部分差异。这一观察结果表明，VH4基因家族的多样性源于核苷酸块的获得，而非点突变的积累。这些核苷酸块可能是通过基因转换或同源重组获得的。所有VH4基因在Asn 60处都有一个潜在的N-连接糖基化位点，一些基因在Asn 52处编码第二个位点。VH4基因家族比之前认为的更大且多态性更高。免疫球蛋白基因多态性可能对免疫反应的遗传变异以及自身免疫性疾病的遗传易感性有重大贡献。
