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

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. [Display omitted] •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 Rhesus and cynomolgus macaques are valuable model organisms for immunological research. Due to the technical difficulties of sequencing the IG loci, the current IG germline gene databases are limited. We applied germline gene inference of expressed antibody repertoires generating comprehensive IGH databases for key sub-groups, furthering genetic analyses of B lymphocyte responses in these species.