Genetically and Functionally Distinct Immunoglobulin Heavy Chain Locus Duplication in Bats.

Area of Science:

• Immunology
• Genetics
• Mammalian Virology

Background:

• The immunoglobulin heavy chain (IgH) locus is vital for adaptive immunity and antibody diversity in vertebrates.
• Bat immune systems are understudied, yet bats serve as reservoirs for numerous viruses, including zoonotic pathogens.
• Understanding bat IgH loci is critical for investigating their unique immunological adaptations and viral resistance.

Purpose of the Study:

• To investigate the genetic structure and function of immunoglobulin heavy chain (IgH) loci in the Vespertilionidae family of bats.
• To characterize the organization and expression of IgH loci in the big brown bat (Eptesicus fuscus).

Main Methods:

• Comparative genomics to analyze IgH locus organization across Vespertilionidae species.
• Single-cell transcriptomics to assess IgH gene rearrangement, expression, and B cell repertoire in Eptesicus fuscus.

Main Results:

• Discovered two complete, functional, and distinct IgH loci on separate chromosomes in Eptesicus fuscus and ten other Vespertilionidae species.
• Confirmed functional rearrangement and expression of both IgH loci in E. fuscus B cells, maintaining allelic exclusion.
• Observed biased usage of the smaller IgH locus and differential selection of B cells and plasma cells based on IgH locus utilization.

Conclusions:

• Bats exhibit a unique mammalian IgH locus organization with two distinct loci on separate chromosomes.
• This novel genetic architecture may contribute to enhanced humoral immunity and viral resistance in bats.
• The findings provide insights into the evolutionary adaptations of bat immune systems and their role in viral pathogenesis.