Antibody repertoire development in fetal and neonatal piglets. XIV. Highly restricted IGKV gene usage parallels the pattern seen with IGLV and IGHV.

Kappa transcripts from fetal piglets were compared to the recently reported kappa genome. Although five IGKV gene families are present in the genome, only IGKV1 and IGKV2 family genes are transcribed; the latter comprises >95% of the repertoire, in which two genes account for ~80%. We provisionally identified a new sequence allele of IGKV2-10 and two new IGKV genes that were not present in the genome of a single Duroc sow. One of these (IGKV2-1) accounted for 39% of the total pre-immune repertoire. The discovery of new IGKV genes and alleles in only 90 transcripts from mixed breeds, suggests considerable polymorphism and polygeny in the kappa locus of swine. Similar to lambda rearrangements, CDR3 length and diversity is restricted. The somatic mutation frequency is low and accumulates in especially CDR1. This transcriptional analysis of the pre-immune kappa repertoire completes a comparative study of all three Ig loci which has allowed the potential and actual combinatorial repertoire to be determined. Calculations show that combinatorial diversity in all three loci contribute comparatively little to the swine pre-immune antibody repertoire. Compared to humans that can potentially generate a million binding site variants, only 16-48 variant comprise 70% of the swine repertoire and 224 account for 95-100%. The frequency of somatic mutation does not differ among rearrangements from all three loci and the CDR3 diversity index shows that swine overwhelmingly generate their pre-immune repertoire by junctional diversity in heavy chain rearrangements.