Characterization of Extensive Diversity in Immunoglobulin Light Chain Variable Germline Genes Across Biomedically Important Mouse Strains

To explore the extent of germline light chain repertoire diversity across mouse strains commonly used in the biomedical sciences, we performed AIRR-seq analysis and germline gene inference for 18 inbred mouse strains, including the four wild-derived strains with diverse sub-species origins. We inferred 1582 IGKV and 63 IGLV sequences, representing 459 and 22 unique IGKV and IGLV sequences. Of the unique inferred germline IGKV and IGLV sequences, 67.8% and 59%, respectively, were undocumented in IMGT. Across strains we observed germline IGKV sequences shared by three distinct IGK haplotypes and a more conserved IGLV germline repertoire. In addition, J gene inference indicated a novel IGK2 allele shared between PWD/PhJ and MSM/MsJ and a novel IGLJ1 allele for LEWES/EiJ and IGLJ2 allele for MSM/MsJ. Finally, a combined IGHV, IGKV, and IGLV phylogenetic analysis of wild-derived germline repertoires displayed reduced germline diversity for the light chain repertoire compared to the heavy chain repertoire, suggesting potential evolutionary differences between the two chains.