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

Immunity. 2021 Feb 9;54(2):355-366.e4. doi: 10.1016/j.immuni.2020.12.018. Epub 2021 Jan 22.

Abstract

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Databases, Genetic
  • Disease Models, Animal
  • Epitopes
  • Genotype*
  • Germ-Line Mutation / genetics*
  • Immunity, Humoral
  • Immunoglobulin Heavy Chains / genetics*
  • Macaca fascicularis
  • Macaca mulatta
  • Phylogeny
  • Polymorphism, Genetic
  • Species Specificity
  • V(D)J Recombination

Substances

  • Epitopes
  • Immunoglobulin Heavy Chains