LAUSR

Significance The enormous diversity of antibodies is a key element to combat infections. Antibodies containing pathogen receptors were a surprising discovery that contrasted antibody diversification through classic recombination events. However, such insert-containing antibodies were thus far exclusively detected in African individuals exposed to malaria parasites and were identified as screening byproducts or through hypothesis-driven search. The prevalence and complexity of insertion events remained elusive. In this study, we devise an unbiased, systematic approach to identify inserts in the human antibody repertoire. We show that inserts from distant genomic regions occur in the majority of donors and are independent of Plasmodium falciparum preexposure. Our findings suggest that four distinct classes of insertion events contribute diversity to the human antibody repertoire.