Novel genes and polymorphisms in human immunoglobulin light chains across diverse populations

The human immunoglobulin light chain loci, kappa (IGK) and lambda (IGL), are complex genomic regions with incompletely defined germline gene content, shaped by extensive duplication and allelic diversity that influence immune function. Here, a comprehensive IMGT annotation of IGK and IGL is presented using two high-quality reference assemblies (GRCh38 and T2T-CHM13), alongside 142 and 125 chromosomal-level haploid assemblies, respectively, representing all major superpopulations. Detailed curation of two assemblies in each locus identified 5 novel IGKV genes (3 functional, 2 pseudogenes), 8 IGKV alleles (3 functional, 5 pseudogenes), 1 novel IGKJ (ORF) allele, 16 novel IGLV genes and 22 novel IGLV alleles (all pseudogenes), validated through read mapping, presence in whole-genome sequencing datasets, and recurrence across assemblies. Structural variation and gene presence/absence patterns were assessed across the entire cohort. IGL displayed high conservation, with recurrent absence observed for only one gene, whereas IGK exhibited greater variability, including the complete loss of the distal region. This structural diversity, allowed us to map potential gene presence/absence patterns across ancestral groups. This work refines the structural resolution of the IGK and IGL, and expands the IMGT reference set, providing an improved framework for studying antibody repertoires, immunogenetic variation, monoclonal antibody development and population-level diversity.