Rhesus and cynomolgus macaque immunoglobulin heavy-chain genotyping yields comprehensive databases of germline VDJ alleles

Rhesus and cynomolgus macaque immunoglobulin heavy-chain genotyping yields comprehensive databases of germline VDJ alleles
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DOI:
10.1016/j.immuni.2020.12.018
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发表时间:
2021-02-09
期刊:
影响因子:
32.4
通讯作者:
Hedestam, Gunilla B. Karlsson
Hedestam, Gunilla B. Karlsson
中科院分区:
医学1区
文献类型:
--
作者:
Bernat, Nestor Vazquez;Corcoran, Martin;Hedestam, Gunilla B. Karlsson

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个体中存在的特定生殖系免疫球蛋白(IG)等位基因的定义是描述抗原特异性抗体应答的个体发生和进化的关键第一步。恒河猴和食蟹猴是临床前研究的重要动物模型,主要使用四个亚组:印度和中国恒河猴以及印度尼西亚和印度尼西亚食蟹猴。我们应用(IG)基因推断工具IgDiscover,并进行了广泛的基于桑格测序的基因组验证,以确定这4个亚组中的生殖系VDJ等位基因,共包括45只猕猴。中国和印度起源的恒河猴之间以及两种猕猴之间存在等位基因重叠,这与大量混合物一致。岛屿限制性猕猴群体显示亚组的等位基因数量最少,但仍保持较高的个体等位基因多样性。这些恒河猴和食蟹猴生殖系IGH等位基因的综合数据库为这些重要的临床前模型中B细胞应答的研究提供了资源。
Definition of the specific germline immunoglobulin (Ig) alleles present in an individual is a critical first step to delineate the ontogeny and evolution of antigen-specific antibody responses. Rhesus and cynomolgus macaques are important animal models for pre-clinical studies, with four main sub-groups being used: Indianand Chinese-origin rhesus macaques and Mauritian and Indonesian cynomolgus macaques. We applied the (Ig) gene inference tool IgDiscover and performed extensive Sanger sequencing-based genomic validation to define germline VDJ alleles in these 4 sub-groups, comprising 45 macaques in total. There was allelic overlap between Chinese- and Indian-origin rhesus macaques and also between the two macaque species, which is consistent with substantial admixture. The island-restricted Mauritian cynomolgus population displayed the lowest number of alleles of the sub-groups, yet maintained high individual allelic diversity. These comprehensive databases of germline IGH alleles for rhesus and cynomolgus macaques provide a resource toward the study of B cell responses in these important pre-clinical models.