Divergent human populations show extensive shared IGK rearrangements in peripheral blood B cells

Abstract

We have analysed the transcribed immunoglobulin kappa (IGK) repertoire of peripheral blood B cells from four individuals from two genetically distinct populations, Papua New Guinean and Australian, using high-throughput DNA sequencing. The depth of sequencing data for each individual averaged 5,548 high-quality IGK reads, and permitted genotyping of the inferred IGKV and IGKJ germline gene segments for each individual. All individuals were homozygous at each IGKJ locus and had highly similar inferred IGKV genotypes. Preferential gene usage was seen at both the IGKV and IGKJ loci, but only IGKV segment usage varied significantly between individuals. Despite the differences in IGKV gene utilisation, the rearranged IGK repertoires showed extensive identity at the amino acid level. Public rearrangements (those shared by two or more individuals) made up 60.2% of the total sequenced IGK rearrangements. The total diversity of IGK rearrangements of each individual was estimated to range from just 340 to 549 unique amino acid sequences. Thus, the repertoire of unique expressed IGK rearrangements is dramatically less than previous theoretical estimates of IGK diversity, and the majority of expressed IGK rearrangements are likely to be extensively shared in individual human beings.