Immunoglobulin heavy chain locus duplication in bats

Bats are major reservoirs of viruses that can be transmitted to humans in zoonotic outbreaks. Antibody-mediated immunity plays an important role in shaping viral evolution and immune evasion but remains understudied in bats. All known mammals have a single immunoglobulin heavy chain (IgH) gene locus and up to two light chain loci. We have identified dual IgH loci on separate chromosomes in 26 bat species, highlighting extreme variation of immunogenetic architecture in order Chiroptera. In a model species, Eptesicus fuscus, we leveraged single-cell transcriptomes to confirm functional rearrangement and expression of both loci, but with different mechanisms for generating antibody diversity and function. These results provide a foundation for analysis of humoral immunity and pathogen response in bats.