New Classes of Insertion Events Driving Human Antibody Diversity Discovered

Using a newly developed technique, a team led by scientists from the Max Delbruck Center for Molecular Medicine has identified different classes of genomic insertion events that contribute to human antibody diversity. In addition to classic recombination events, antibody-containing pathogen receptors were recently found to contribute to human antibody diversification. However, such insert-containing antibodies were only detected in African individuals exposed to malaria parasites. To better understand the prevalence and complexity of insertion events, the researchers devised an unbiased, systematic approach to identify ectopic inserts in human antibody transcripts. As reported in the Proceedings of the National Academy of Sciences this week, they use the method to show that inserts from distant genomic regions occur in the majority of a genetically diverse cohort, independent of preexposure to malaria parasites. "Contrasting the classic recombination by predefined segments and addition of random nucleotides, our data suggest that ectopic inserts can contribute another layer of diversity forming the human antibody repertoire," the study's authors write.