New alleles of IGKV genes A2 and A18 suggest significant human IGKV locus polymorphism

The human kappa light chain consists of approximately 35 potentially functional IGKV genes. However, an estimation of the diversity in the IGKV repertoire of an individual will be affected by the extent of polymorphisms for the different IGKV genes and their patterns of inheritance. To date, little information is available to indicate the extent of allelic variation of the IGKV genes. We examined the extent of allelism for one IGKV gene pair, the distal region A2 gene and its closely related proximal region duplicate A18. We found two new alleles for A2 and one new allele for A18, and sequenced approximately 1 kilobase flanking each gene. The new A18 allele, unlike the originally described allele, appears to be functional. All these alleles were found at relatively high frequencies in the four ethnic populations studied, with the exception of the defective A2b allele which was highly represented only in Navajos. The originally described A2a allele encodes for the predominant protective antibody against Haemophilus influenzae. Therefore, the patterns of allelic inheritance described for this IGKV gene pair indicate that allelism in the IGKV locus is likely to have a significant impact on immune responses.