Urbana High School, Ijamsville, MD 21754, USA; BSP CCR Genetics Core, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA; Werner H. Kirsten Student Intern Program, National Cancer Institute (NCI)-Frederick, National Institutes of Health (NIH), Frederick, MD 21702-1201, USA.
Exp Mol Pathol. 2013 Dec;95(3):357-63. doi: 10.1016/j.yexmp.2013.10.004. Epub 2013 Oct 21.
The vast diversity of antibody repertoires is largely attributed to heavy chain (V(H)) recombination of variable (V), diversity (D) and joining (J) gene segments. We used 454 sequencing information of the variable domains of the antibody heavy chain repertoires from neonates, normal adults and an HIV-1-infected individual, to analyze, with Circos software, the VDJ pairing patterns at birth, adulthood and a time-dependent response to HIV-1 infection. Our comparative analyses of the Ig VDJ repertoires from these libraries indicated that, from birth to adulthood, VDJ recombination patterns remain the same with some slight changes, whereas some V(H) families are selected and preferentially expressed after long-term infection with HIV-1. We also demonstrated that the immune system responds to HIV-1 chronic infection by selectively expanding certain HV families in an attempt to combat infection. Our findings may have implications for understanding immune responses in pathology as well as for development of new therapeutics and vaccines.
抗体库的巨大多样性在很大程度上归因于重链（V（H））可变（V）、多样性（D）和连接（J）基因片段的重组。我们使用来自新生儿、正常成年人和 HIV-1 感染者的抗体重链库的 454 测序信息，利用 Circos 软件分析出生时、成年时和对 HIV-1 感染的时间依赖性反应的 VDJ 配对模式。我们对这些文库中 Ig VDJ 库的比较分析表明，从出生到成年，VDJ 重组模式保持不变，略有变化，而某些 V（H）家族在长期感染 HIV-1 后被选择并优先表达。我们还表明，免疫系统通过选择性地扩增某些 HV 家族来对 HIV-1 慢性感染作出反应，以试图抵抗感染。我们的发现可能对理解病理学中的免疫反应以及开发新的治疗方法和疫苗具有重要意义。
