Genomic variation in the porcine immunoglobulin lambda variable region

Abstract

Production of a vast antibody repertoire is essential for protection against pathogens. Variable region germline complexity contributes to repertoire diversity and is a standard feature of mammalian immunoglobulin loci, but functional V region genes are limited in swine. For example, the porcine lambda light chain locus is composed of 23 variable (V) genes and 4 joining (J) genes, but only 10 or 11 V and 2 J genes are functional. Allelic variation in V and J may increase overall diversity within a population, yet lead to repertoire holes in individuals lacking key alleles. Previous studies focused on heavy chain genetic variation, thus light chain allelic diversity is not known. We characterized allelic variation of the porcine immunoglobulin lambda variable (IGLV) region genes. All intact IGLV genes in 81 pigs were amplified, sequenced, and analyzed to determine their allelic variation and functionality. We observed mutational variation across the entire length of the IGLV genes, in both framework and complementarity determining regions (CDRs). Three recombination hotspots were also identified, suggesting that non-allelic homologous recombination is an evolutionarily alternative mechanism for generating germline antibody diversity. Functional alleles were greatest in the most highly expressed families, IGLV3 and IGLV8. At the population level, allelic variation appears to help maintain the potential for broad antibody repertoire diversity in spite of reduced gene segment choices and limited germline sequence modification. The trade-off may be a reduction in repertoire diversity within individuals that could result in increased variation in immunity to infectious disease and response to vaccination.

A Cell Proliferation and Inflammatory Signature Is Induced by Lawsonia intracellularis Infection in Swine

“…Around half of the 23 DEGs of high-lesion animals at 28 dpi were only found at that time point. Several of these genes encode proteins involved in antibody biosynthesis, including IGLC1 , which encodes the constant region of immunoglobulins, and IGLV-10 and IGLV-12 , which encode the variable regions of the lambda light chain of immunoglobulins (18). The only gene with a decreased level of transcripts in animals with high lesions at 28 dpi was CA1 , which codes for carbonic anhydrase 1 (19).…”

The major histocompatibility complex homozygous inbred Babraham pig as a resource for veterinary and translational medicine

“…For the pig major histocompatibility complex (MHC, also referred to as swine leukocyte antigen [SLA]), there are currently 238 MHC class I alleles and 223 MHC class II alleles described for Sus scrofa in the Immuno‐Polymorphism Database (IPD)‐MHC database (http://www.ebi.ac.uk/ipd/mhc/group/SLA). The antibody lambda locus also appears to be highly polymorphic, even among commercial pigs with a similar genetic background, and the T‐cell loci appear variable in gene content, at least between breeds (Schwartz, J.C., T. Connelley, and J.A. Hammond, unpublished).…”

Viral Infection Skews Immunoglobulin Light Chain Repertoire Diversity

“…As shown in Figure 2, there is a notably high level of sequence divergence in IGK transcripts from the germline annotation of the 14 most C-proximal IGKV genes in the locus (9). Since a high degree of heterozygosity was present, it is possible that individual diversity may be due to allelic variation, as has been shown in IGLV genes (11, 12). Allelic variation also has been shown in humans to significantly affect repertoire diversity (24, 25).…”

“…The porcine lambda locus possess two functional IGLJ genes and 12 putatively functional IGLV genes belonging to three families, of which the IGLV3 and IGLV8 families comprise the vast majority of known expression (9, 10). We also previously identified substantial allelic variation among the germline IGLV (11) and described IGLV3-6 which is present in some animals as either a pseudogene or as a functional highly expressed gene (12).…”