百万碱基对人类免疫球蛋白基因座的功能性移植在小鼠中重现了人类抗体反应。
Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice.
作者信息
Mendez M J, Green L L, Corvalan J R, Jia X C, Maynard-Currie C E, Yang X D, Gallo M L, Louie D M, Lee D V, Erickson K L, Luna J, Roy C M, Abderrahim H, Kirschenbaum F, Noguchi M, Smith D H, Fukushima A, Hales J F, Klapholz S, Finer M H, Davis C G, Zsebo K M, Jakobovits A
机构信息
Abgenix, Inc., Fremont, California 94555, USA.
出版信息
Nat Genet. 1997 Feb;15(2):146-56. doi: 10.1038/ng0297-146.
We constructed two megabase-sized YACs containing large contiguous fragments of the human heavy and kappa (kappa) light chain immunoglobulin (Ig) loci in nearly germline configuration, including approximately 66 VH and 32 V kappa genes. We introduced these YACs into Ig-inactivated mice and observed human antibody production which closely resembled that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enables the mice to generate high affinity fully human antibodies to multiple antigens, including human proteins. Our results underscore the importance of the large Ig fragments with multiple V genes for restoration of a normal humoral immune response. These mice are likely to be a valuable tool for the generation of therapeutic antibodies.
我们构建了两个大小为兆碱基的酵母人工染色体（YAC），其包含几乎处于种系构型的人类重链和κ轻链免疫球蛋白（Ig）基因座的大片段连续片段，包括约66个VH基因和32个Vκ基因。我们将这些YAC导入Ig失活的小鼠中，并观察到人类抗体的产生，其在所有方面都与人类中所见的极为相似，包括基因重排、组装和库。多样的Ig基因使用以及体细胞超突变使小鼠能够产生针对多种抗原（包括人类蛋白质）的高亲和力全人源抗体。我们的结果强调了带有多个V基因的大Ig片段对于恢复正常体液免疫反应的重要性。这些小鼠可能是生成治疗性抗体的宝贵工具。
Zotero 插件