Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire.

ABSTRACT: Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which have not been fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate that polymorphisms within the immunoglobulin heavy chain locus (IGH) impact the naive and antigen-experienced antibody repertoire, indicating that genetics predisposes individuals to mount qualitatively and quantitatively different antibody responses. We pair recently developed long-read genomic sequencing methods with antibody repertoire profiling to comprehensively resolve IGH genetic variation, including novel structural variants, single nucleotide variants, and genes and alleles. We sho

SUBMITTER: Rodriguez OL 

PROVIDER: S-EPMC10362067 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature