Adderson E E, Azmi F H, Wilson P M, Shackelford P G, Carroll W L
Department of Pediatrics, University of Utah, Salt Lake 84112.
J Immunol. 1993 Jul 15;151(2):800-9.
We have previously shown that human antibody (Ab) directed against the capsular polysaccharide of the important bacterial pathogen, Haemophilus influenzae type b (Hib) is encoded by a small group of VH3 gene family members. The majority of anti-Hib PS Ab use members of the smaller VH3b subfamily. To examine directly the available human VH3 repertoire, we have used PCR to amplify and clone candidate germ-line VH3b H chain V region genes from two unrelated subjects from whom anti-Hib polysaccharide mAb had been previously obtained. A single functional VH3b germ-line gene was obtained from one subject. This gene is identical throughout the coding region to the previously identified gene 9.1. Twelve distinct VH3b germ-line sequences, 87.6-99.8% homologous to one another, were obtained from the second subject. One of these genes, LSG1.1, is also identical to the 9.1 germ-line gene, and a second, LSG6.1, is identical to a previously reported cDNA, M85. These germ-line VH3b genes are 82.7-94.1% homologous to rearranged anti-Hib PS VH3b segments obtained from these subjects. Our findings further demonstrate that considerable polymorphism of VH segments exists in the human population. Despite the presence of very highly homologous VH elements in the germ line, particular genes are highly conserved within the outbred human population.
我们之前已经表明，针对重要细菌病原体b型流感嗜血杆菌（Hib）荚膜多糖的人抗体（Ab）由一小群VH3基因家族成员编码。大多数抗Hib PS Ab使用较小的VH3b亚家族成员。为了直接检测可用的人VH3库，我们使用聚合酶链反应（PCR）从两个无关个体中扩增并克隆候选种系VH3b重链V区基因，之前已从这两个个体中获得抗Hib多糖单克隆抗体（mAb）。从一个个体中获得了一个功能性VH3b种系基因。该基因在整个编码区与先前鉴定的基因9.1相同。从第二个个体中获得了12个不同的VH3b种系序列，它们彼此之间的同源性为87.6% - 99.8%。其中一个基因LSG1.1也与9.1种系基因相同，另一个基因LSG6.1与先前报道的cDNA M85相同。这些种系VH3b基因与从这些个体中获得的重排抗Hib PS VH3b片段的同源性为82.7% - 94.1%。我们的研究结果进一步证明，人类群体中VH片段存在相当大的多态性。尽管种系中存在高度同源的VH元件，但特定基因在远交人群中高度保守
