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Published on: February 3, 2013
The evolutionary and functional significance of germline immunoglobulin gene variation
Matt Pennell1, Oscar L Rodriguez2, Corey T Watson2
1Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA; Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
Abstract:
The recombination between immunoglobulin (IG) gene segments determines an individual's naïve 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 germline variants and immunophenotype raise the question on the evolutionary causes and consequences of diversity within IG loci. We discuss why the extreme diversity 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.
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