Germline polymorphisms in the immunoglobulin kappa and lambda loci underpinning antibody light chain repertoire variability.

ABSTRACT: Variation in antibody (Ab) responses contributes to variable disease outcomes and therapeutic responsiveness, the determinants of which are incompletely understood. This study demonstrates that polymorphisms in immunoglobulin (IG) light chain loci dictate the composition of the Ab repertoire, establishing fundamental baseline differences that influence functional Ab-mediated responses. Using long-read genomic sequencing of the IG kappa (IGK) and IG lambda (IGL) loci, we resolve genetic variation, including structural variants, single nucleotide variants, and gene alleles. By integrating these genetic data with Ab repertoire profiling, we find that all forms of IG germline variation contribute to inter-individual gene usage differences for >70% of light chain genes in the repertoire, direct

SUBMITTER: Engelbrecht E 

PROVIDER: S-EPMC12753720 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature