The evolutionary and functional significance of germline immunoglobulin gene variation

The recombination between immunoglobulin (IG) gene segments determines an individual's naive antibody repertoire and, consequently, (auto)antigen recognition. Emerging evidence suggests that mammalian IG germline variation impacts humoral immune responses associated with vaccination, infection, and autoimmunity - from the molecular level of epitope specificity, up to profound changes in the architecture of antibody repertoires. These links between IG germ-line variants and immunophenotype raise the question on the evolutionary causes and consequences of diversity within IG loci. We discuss why the extreme diver-sity in IG loci remains a mystery, why resolving this is important for the design of more effective vaccines and therapeutics, and how recent evidence from multiple lines of inquiry may help us do so.

Automated summary

The recombination between immunoglobulin gene segments determines an individual's antibody repertoire and impacts immune responses. The diversity within immunoglobulin loci remains a mystery but is important for designing effective vaccines and therapeutics. Recent evidence may help unravel the causes and consequences of this diversity.