In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 8, No. 81 ( 2023-03-31)
Abstract:
Insertions and deletions (indels) are genomic DNA alterations that are critical to the emergence of a long complementarity determining region 3 (CDR3), which is a key step during immunoglobulin diversification. Indels have been notoriously difficult to detect, thus making it difficult to define mechanisms involved in this process. Hao et al . developed passenger-immunoglobulin mouse models to carry out ultra-deep profiling of indels. They observed that activation-induced cytidine deaminase (AID)–dependent ±1 bp indel events were the most common and involved base excision repair. In contrast, longer in-frame indels, such as those associated with CDR3 lengthening, were rare and required other DNA processing molecules. They were also able to increase indel frequencies through ectopic expression of a DNA exonuclease or changes in the balance of DNA polymerases, thus suggesting a method for generating antibodies with enhanced neutralization. —CNF
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.ade1167
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2023
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