Genomic Structure of Porcine Immunoglobulin Heavy Chain Constant Region

Variation of locus numbers of immunoglobulin heavy chain constant regions (IGHCs) is observed among mammals; human and mouse have four subclasses of IgG and rabbit has 13 subclasses of IgA. Such expansion of the particular IGHCs is considered to occur after speciation, and each IGHC confers different biological characteristic on immunoglobulin. Previous studies based on cDNA analyses suggested that pig has 6 to 11 subclasses of IgG. To annotate IGHC subclasses in swine, we cloned and sequenced the entire genomic region containing porcine IGHCs. Three BAC clones isolated from our porcine genomic library were completely sequenced. The sequences of each overlapped region between the clones were identical, showing that the three clones were derived from a single haplotype. The contiguous sequence of the clones carried D segment genes of IgH and TREM121 gene, which flank the region carrying IGHCs in human genome, suggesting that the determined sequence covered the whole genomic region containing porcine IGHCs. The genomic region containing porcine IGHCs was about 190kb, showing good agreement with those of other mammals. We found six IgG IGHCs and each of IgM, IgD, IgE and IgA in the region. All observed IgG IGHCs formed a cluster between IGHCs of IgD and IgE. IgG3, the most ancient IgG subclass, was located at the beginning of the IgG cluster. Furthermore, both IgG5a and IgG5b IGHCs were detected in the determined sequence, suggesting that IgG5a and IgG5b are not derived from allelic variation but are encoded by different loci.