The B cell subtypes and VDJ repertoire of young adult rhesus macaques.

Abstract

Rhesus macaques (RMs) are widely employed as a preclinical model in vaccination and infectious disease studies, yet their B cell immunobiology and immunogenetics remain ill-characterized. In this study, single-cell RNA/VDJ sequencing was conducted on peripheral blood mononuclear cell samples from 6 RMs to describe the transcriptomic and V(D)JC repertoires of B cells and subtypes. Twelve RM B cell clusters of distinct transcriptional states were identified, including IgM+ memory B cells (MBCs), class-switched MBCs, CD11c+ MBCs, and activated B cells. Novel gene signatures were also characterized for each B cell subtype, such as FCRL2 and CD24 for circulating marginal zone-like B cells. In addition, VDJ repertoire properties of the global B cell population and each B cell subtype were elucidated, including IGH/K/L-V(D)JC gene family and subtype usage, class-switch recombination status, somatic hypermutation rate and levels, CDRH3 amino acid length, and CDRH3 amino acid hydrophobicity scores. Interesting insights included the 1:1 ratio of kappa and lambda light chain usage and a preferential decreased IGHV3 but increased IGHV1 and 5 gene family usage in IGHG1 than IGHM-bearing B cells. Altogether, this study through comprehensive transcriptomic analyses identifies 12 distinct RM B cell subtypes paired with their respective V(D)JC repertoire, unraveling the complexity of B cell heterogeneity and improving future preclinical studies that can translate insights from this important nonhuman primate model to the understanding of human immunobiology.