Germline polymorphisms in the immunoglobulin kappa and lambda loci explain variation in the expressed light chain antibody repertoire.

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 preclude functional Ab-mediated responses. Using long-read genomic sequencing of the IG kappa (IGK) and IG lambda (IGL) loci, we comprehensively resolved genetic variation, including novel structural variants, single nucleotide variants, and gene alleles. By integrating these genetic data with Ab repertoire profiling, we found that all forms of IG germline variation contributed to inter-individual gene usage differences for >70% of light chain genes i

SUBMITTER: Engelbrecht E 

PROVIDER: S-EPMC12154815 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature