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Abstract The genetic locus encoding immunoglobulin heavy chains (IgH) is critical for vertebrate humoral immune responses and diverse antibody repertoires. Immunoglobulin and T cell receptor loci of most bat species have not been annotated, despite the recurrent role of bats as viral reservoirs and sources of zoonotic pathogens. We investigated the genetic structure and function of IgH loci across the largest bat family, Vespertilionidae, focusing on big brown bats(Eptesicus fuscus). We discovered thatE. fuscusand ten other species within Vespertilionidae have two complete, functional, and distinct immunoglobulin heavy chain loci on separate chromosomes. This locus organization is previously unknown in mammals, but is reminiscent of more limited duplicated loci in teleost fish. Single cell transcriptomic data validate functional rearrangement and expression of immunoglobulin heavy chains of both loci in the expressed repertoire ofEptesicus fuscus, with maintenance of allelic exclusion, bias of usage toward the smaller and more compact IgH locus, and evidence of differential selection of antigen-experienced B cells and plasma cells varying by IgH locus use. This represents a unique mechanism for mammalian humoral immunity and may contribute to bat resistance to viral pathogenesis.
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This content will become publicly available on April 16, 2026
Back to basics: Immunoglobulin germline reference sequences enable investigations and reveal insights into bat-specific immunity
Summary We generated a highly-contiguous, annotated genome of the Jamaican fruit bat,Artibeus jamaicensis,including annotated germline immunoglobulin heavy chain (IGH) and light chain (IGL) loci to understand bat B cell receptor repertoires. The bat germline shares many structures and features described in human immunoglobulin loci. However, some features are unique toA. jamaicensis, including an expansion of cysteine-rich IGHV genes. To investigate the relationship between the germline IGH locus and expressed B cell receptors (BCRs), we sequenced the BCRs of wild-caught and captiveA. jamaicensis, finding an enrichment of IGHV3 and IGHV4 genes. Compared to humans,A. jamaicensishad shorter CDRH3s and lower levels of somatic hypermutation. Our results demonstrate that while immunoglobulin loci are largely conserved between bats and humans, distinct differences exist in the bat germline, highlighting the need for more detailed genetic characterization of these mammals.
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- Award ID(s):
- 2032157
- PAR ID:
- 10637367
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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