Gene discovery and expression analysis of the B cell receptor repertoire in the domestic ferret model

The domestic ferret is the preferred model organism for the study of influenza A infection and responses to vaccination, because its respiratory tract architecture and sialic acid receptor type and distribution are similar to those in humans. Despite this, the ferret has remained underutilized in antibody-omics research, which is increasingly critical to inform vaccine design. The molecular analysis of antibody responses is predicated on precise knowledge of the germline V(D)J segments, and is an active area of research for this species. To define a reference immunoglobulin repertoire for the ferret, we used a curated set of V(D)J genes from human and closely related carnivores to BLAST the ferret genome. Non-overlapping BLAST hits were annotated and vetted for recombination signal sequences as well as segment-specific functionality as defined by IMGT. Immunoglobulin transcript expression was analyzed for both variable and constant region genes, and we identified two functional IGHG genes in the ferret. We report a publicly available workflow for annotating immunoglobulin genes in any species, as well as a complete ferret immunoglobulin gene set. We include the genomic sequences for 409 ferret immunoglobulin genes of both the heavy and light chains. This reference data set establishes a critically important foundation for future BCR and antibody repertoire studies in this established preclinical vaccine model.