Sequencing of non-VDJ insertions in human antibody transcripts

DNA recombination in B cells involving distant genomic loci can contribute a foreign antigen-binding element to form a hybrid antibody with broad reactivity for Plasmodium falciparum. So far, antibodies containing the extracellular domain of the LAIR1 receptor represent a unique example of cross-chromosomal antibody diversification. Here, we devise a technique to profile non-VDJ elements from distant genes in human antibody transcripts. We show that insertions in heavy, but not light chains, are prevalent across the population, independent of exposure to the malaria parasite and occur at frequencies between 1 in 104-106 B cells.