Immunity
Volume 54, Issue 2, 9 February 2021, Pages 355-366.e4
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Rhesus and cynomolgus macaque immunoglobulin heavy-chain genotyping yields comprehensive databases of germline VDJ alleles

https://doi.org/10.1016/j.immuni.2020.12.018Get rights and content
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Highlights

  • Macaque germline gene inference identifies several hundred novel IGV alleles

  • Rhesus and cynomolgus macaques display overlapping IGV allelic content

  • Analysis of macaque IGV germline genes suggests frequent structural variation

  • Comprehensive IG databases are essential for analysis of somatic hypermutation

Summary

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: Indian- and 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.

Keywords

immunoglobulin
antibody
germline genes
database
rhesus macaques
cynomolgus macaques
heavy chain
allelic diversity

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