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| Item Type: | Article |
|---|---|
| Title: | Different classes of genomic inserts contribute to human antibody diversity |
| Creators Name: | Lebedin, M., Foglierini, M., Khorkova, S., Vázquez García, C., Ratswohl, C., Davydov, A.N., Turchaninova, M.A., Daubenberger, C., Chudakov, D.M., Lanzavecchia, A. and de la Rosa, K. |
| Abstract: | Recombination of antibody genes in B cells can involve distant genomic loci and contribute a foreign antigen-binding element to form hybrid antibodies with broad reactivity for Plasmodium falciparum. So far, antibodies containing the extracellular domain of the LAIR1 and LILRB1 receptors represent unique examples of cross-chromosomal antibody diversification. Here, we devise a technique to profile non-VDJ elements from distant genes in antibody transcripts. Independent of the preexposure of donors to malaria parasites, non-VDJ inserts were detected in 80% of individuals at frequencies of 1 in 10(4) to 10(5) B cells. We detected insertions in heavy, but not in light chain or T cell receptor transcripts. We classify the insertions into four types depending on the insert origin and destination: 1) mitochondrial and 2) nuclear DNA inserts integrated at VDJ junctions; 3) inserts originating from telomere proximal genes; and 4) fragile sites incorporated between J-to-constant junctions. The latter class of inserts was exclusively found in memory and in in vitro activated B cells, while all other classes were already detected in naïve B cells. More than 10% of inserts preserved the reading frame, including transcripts with signs of antigen-driven affinity maturation. Collectively, our study unravels a mechanism of antibody diversification that is layered on the classical V(D)J and switch recombination. |
| Keywords: | B Cell Diversity, Antibody Repertoire, Insert |
| Source: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Volume: | 119 |
| Number: | 36 |
| Page Range: | e2205470119 |
| Date: | 6 September 2022 |
| Official Publication: | https://doi.org/10.1073/pnas.2205470119 |
| PubMed: | View item in PubMed |
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