Characterization of the Peromyscus leucopus immunoglobulin germline repertoire and anti-OspA antibody response reveals conserved germline IGHV features among cricetid rodents

ABSTRACT Peromyscus leucopus ( P. leucopus ) is an important reservoir host for several zoonoses, including Borrelia burgdorferi ( B. burgdorferi ), the causative agent of Lyme disease. However, the immunoglobulin germline repertoire underlying antibody responses in this reservoir host remains poorly defined. In this study, we characterized the immunoglobulin variable genes of P. leucopus and identified 12 IGHV, 12 IGKV, and 3 IGLV gene families comprising 129, 87, and 12 genes, respectively. These genes exhibited similar usage patterns to those of Mus musculus ( M. musculus ). We also identified a high-divergence region (HDR) within the germline IGHV loci of three Borrelia sp.-susceptible Cricetidae species, P. leucopus , Peromyscus maniculatus ( P. maniculatus ), and Arvicola amphibius ( A. amphibius ). Compared with the corresponding regions in Muridae species, the Cricetidae HDRs are expanded and contain a large number of IGHV genes. To investigate the antigen-specific features of the repertoire, we analyzed the antibody responses of P. leucopus to B. burgdorferi outer surface protein A (OspA), a highly immunogenic tick midgut adhesin involved in midgut colonization. Comparative analysis of more than 140 IGHV genes from immunized P. leucopus showed that germline IGHV genes encoding anti-OspA antibodies exhibited higher sequence similarity to corresponding germline IGHV genes in P. maniculatus and A. amphibius than did P. leucopus germline IGHV genes not associated with anti-OspA responses. IMPORTANCE This study characterized the immunoglobulin gene repertoire of Peromyscus leucopus and revealed extensive diversity across its variable-region loci. Analysis of antibody response to outer surface protein A (OspA) showed that germline IGHV genes encoding anti-OspA antibodies showed higher sequence similarity to their corresponding germline IGHV genes in other Borrelia -susceptible cricetid rodents, suggesting that conserved germline IGHV features are associated with OspA recognition. These findings lay the foundation for further understanding of antibody responses in this important reservoir host.