The individual and population genetics of antibody immunity

Watson, Corey T.; Glanville, Jacob; Marasco, Wayne A.

Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B cell development and mutations during affinity maturation, the germline IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype-phenotype correlations between specific IG germline variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored. Here we outline interconnections between IG genomic diversity and Ab expressed repertoires and structure. We further propose a strategy for integrating IG genotyping with functional Ab profiling data as a means to better predict and optimize humoral responses in genetically diverse human populations, with immediate implications for personalized medicine.