Immunoglobulin heavy chain locus duplication in bats 4518

Abstract Description Bats are significant reservoir hosts of viruses, yet their antibody-mediated immunity, a key factor in shaping viral evolution and immune evasion, remains understudied. Unlike all other known mammals that possess a single immunoglobulin heavy chain (IgH) locus, we have identified dual, complete, and functional IgH loci on separate chromosomes in eleven bat species. This immunogenetic architecture is reminiscent of more limited duplicated loci in teleost fish but is novel among mammals. Using single-cell transcriptomic data from Eptesicus fuscus (big brown bats), we confirm functional rearrangement and expression of both IgH loci. These loci exhibit distinct mechanisms for generating antibody diversity and function, including biased usage favoring the smaller, more compact locus, and differential selection in antigen-experienced B cells and plasma cells. These findings reveal a unique adaptation in mammalian humoral immunity, offering new insights into the antibody responses in bats, the functional specialization of their humoral immunity and its potential role in resistance to viral pathogenesis. Funding Sources Supported by NSF IOS 2032157; NSF BII 2021909; NSF BII 2213854; NIH T32OD011121; NIH 5 T32 AI07290; NIH NIAID 5 R21 AI169548; LSRF; Open Phil; Stanford Woods Institute for the Environment EVP; Stanford CEHG Postdoctoral Fellowship; Stanford School of Medicine Dean’s Postdoctoral Fellowship, funds from the Stanford Pathology Department and an endowment from the Crown Fndn. Topic Categories Veterinary and Comparative Immunology (VET)