Revisiting the Pig IGHC Gene Locus in Different Breeds Uncovers Nine Distinct IGHG Genes

Area of Science:

• Immunology
• Genomics
• Comparative Mammalian Genetics

Background:

• Immunoglobulin G (IgG) subclass diversification is crucial for adaptive immunity in placental mammals.
• While well-studied in humans and mice, the genomic and functional diversity of porcine IgG subclasses remains incompletely understood.
• Pigs are agriculturally and biomedically significant, making their immune system a key research area.

Purpose of the Study:

• To characterize and map the immunoglobulin heavy (IgH) C region gene locus in indigenous Chinese pig breeds and Duroc.
• To identify variations in IgG subclass gene copy numbers and sequences among different pig breeds.
• To establish a foundation for investigating the structure-function relationships of porcine IgG subclasses.

Main Methods:

• Bacterial artificial chromosome sequencing was employed to analyze the IgH C region.
• Newly assembled genomes generated by PacBio sequencing were utilized.
• Phylogenetic analysis was performed to classify porcine IgG heavy chain constant region genes (IGHG).
• A mouse monoclonal antibody (mAb) specific for IgG3 was developed.

Main Results:

• Significant differences were observed in IGHG gene numbers among Chinese pig breeds (Erhualian: 7 genes, Xiang: 5 genes) and Duroc (6 genes).
• Other immunoglobulin genes (IGHM, IGHD, IGHA, IGHE) were found to be single copy and conserved across examined pig breeds.
• Porcine IGHG genes were phylogenetically classified into nine subclasses: IGHG1, IGHG2a, IGHG2b, IGHG2c, IGHG3, IGHG4, IGHG5a, IGHG5b, and IGHG5c.
• A mouse monoclonal antibody specific for IgG3 was successfully developed.

Conclusions:

• The study reveals significant genomic diversification of IGHG genes in pigs, contrasting with conserved IgM, IgD, IgA, and IgE genes.
• The identified nine porcine IgG subclasses provide a framework for future functional immunogenetic studies.
• This research offers a crucial starting point for understanding the structure-function relationship of IgG subclasses in pigs.