Repertoire comparison of the B-cell receptor encoding loci in humans and rhesus macaques by next generation sequencing

Authors: VIGDOROVICH, VLADIMIR - Center For Infectious Disease Research; OLIVER, BRIAN - Center For Infectious Disease Research; CARBONETTI, SARA - Center For Infectious Disease Research; DAMBRAUSKAS, NICHOLAS - Center For Infectious Disease Research; Lange, Miles; YACOOB, CHRISTINA - Fred Hutchinson Cancer Research Center; LEAHY, WILL - Mazama Science; CALLAHAN, JONATHAN - Mazama Science; STAMATATOS, LEONIDAS - Fred Hutchinson Cancer Research Center; SATHER, D. NOAH - Center For Infectious Disease Research

Submitted to: Clinical and Translational Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/16/2016
Publication Date: 7/22/2016
Citation: Vigdorovich, V., Oliver, B.G., Carbonetti, S., Dambrauskas, N., Lange, M.D., Yacoob, C., Leahy, W., Callahan, J., Stamatatos, L., Sather, D. 2016. Repertoire comparison of the B-cell receptor encoding loci in humans and rhesus macaques by next generation sequencing. Clinical and Translational Immunology. 5.

Interpretive Summary: Rhesus macaques are the most widely used non-human primate model for biomedical research, which includes studies on microbial pathogenesis, host-pathogen interaction and drug or vaccine efficacy. To better understand the development of adaptive immunity in humans and macaques; sequence analysis of their circulating B cell repertoires was conducted. Next generation sequencing technology can now facilitate the comprehensive study of selectively isolated B cells at different life stages. The analyses of immunoglobulin gene segments suggest inherent similarities and differences occur during human and macaque B cell maturation. The implications of this study and the use of non-human primates as a model system are discussed.

Technical Abstract: Rhesus macaques are a widely used model system for the study of vaccines, infectious diseases, and microbial pathogenesis. Their value as a model lies in their close evolutionary relationship to humans, which, in theory, allows them to serve as a close approximation of the human immune system. However, despite their prominence as a human surrogate model system, many aspects of the rhesus macaque immune system remain ill-characterized. In particular, B-cell-mediated immunity in macaques has not been sufficiently characterized, and the B cell receptor-encoding loci have not been thoroughly annotated. To address these gaps, we analyzed the circulating heavy- and light-chain repertoires in humans and rhesus macaques by next generation sequencing. By comparing V gene segment usage, J segment usage, and CDR3 lengths between the two species we identified several important similarities and differences. These differences were especially notable in the IgM+ B cell repertoire. However, the class-switched, antigen-educated B-cell populations converged on a set of similar characteristics, implying similarities in how each species responds to antigen. Our study provides the first comprehensive overview of the circulating repertoires of the heavy- and light- chain sequences in rhesus macaques, and provides insight into how they may perform as a model system for B-cell mediated immunity in humans.