Unique Features of Immunity within the Immunoglobulin Heavy Chain Locus of Egyptian Rousette Bats

Abstract

Abstract The Egyptian fruit bat (Rousettus aegyptiacus, ERB) is reported to be the reservoir of Marburg virus (MARV). Indeed, MARV infection is almost completely asymptomatic in ERBs while eliciting a severe hemorrhagic fever in humans and non-humans primates (NHPs). To understand the biological mechanisms that explain these differential outcomes to MARV, we aim to investigate the differences between both animals’ immune systems. One of the antiviral mechanisms to control viruses is the humoral response. The B cell receptor (BCR) is composed of two heavy and two light chains heterodimers. Both immunoglobulin (Ig) chains undergo DNA rearrangement to generate a diverse repertoire, crucial for diverse antigenic recognition. The Ig heavy chain locus is comprised of the variable (V), diversity (D), joining (J), and constant (C) genes. Utilizing high throughput sequencing to resolve the V(D)J rearrangements we can characterize the BCR repertoire and define the clonotypes that are generated in response to vaccination or infection. To define the BCR repertoire with DNA sequencing, a thorough representation of the Ig heavy chain (IGH) locus is necessary. We were able to resolve on contiguous IGH locus containing all BCR genes that were previously on 21 different scaffolds. In addition, we identified a unexpected expansion of IgE genes not described in another species to date. We defined the tissue expression of these novel IgE genes as well as IgGs, IgA, and IgM. Finally, we predicted differential functions between subclasses in silico. These data support unique immune response capabilities of ERBs that may aid in their control of pathogenic human viruses.