| Literature DB >> 26582132 |
Leng-Siew Yeap1, Joyce K Hwang1, Zhou Du1, Robin M Meyers1, Fei-Long Meng1, Agnė Jakubauskaitė1, Mengyuan Liu1, Vinidhra Mani1, Donna Neuberg2, Thomas B Kepler3, Jing H Wang1, Frederick W Alt4.
Abstract
In activated B lymphocytes, AID initiates antibody variable (V) exon somatic hypermutation (SHM) for affinity maturation in germinal centers (GCs) and IgH switch (S) region DNA breaks (DSBs) for class-switch recombination (CSR). To resolve long-standing questions, we have developed an in vivo assay to study AID targeting of passenger sequences replacing a V exon. First, we find AID targets SHM hotspots within V exon and S region passengers at similar frequencies and that the normal SHM process frequently generates deletions, indicating that SHM and CSR employ the same mechanism. Second, AID mutates targets in diverse non-Ig passengers in GC B cells at levels similar to those of V exons, definitively establishing the V exon location as "privileged" for SHM. Finally, Peyer's patch GC B cells generate a reservoir of V exons that are highly mutated before selection for affinity maturation. We discuss the implications of these findings for harnessing antibody diversification mechanisms.Entities:
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Year: 2015 PMID： 26582132 PMCID： PMC4751889 DOI： 10.1016/j.cell.2015.10.042
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582