Journal
JOURNAL OF IMMUNOLOGY
Volume 172, Issue 6, Pages 3382-3384Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.172.6.3382
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A feature of Ig hypermutation is the presence of hypermutable DNA sequences that are preferentially found in the V regions of Ig genes. Among these, RGYW/WRCY is the most pronounced motif (G.-C is a mutable position; R = A/G, Y = C/T and W = A/T). However, a molecular basis for the high mutability of RGYW was not known until recently. The discovery that activation-induced cytidine deaminase targets the DNA encoding V regions, has enabled the analysis of its targeting properties when expressed outside of the context of hypermutation. We analyzed these data and found evidence that activation-induced cytidine deaminase is the major source of the RGYW mutable motif, but with a new twist: DGYW/WRCH (G:C is the mutable position; D = A/G/T, H = T/C/A) is a better descriptor of the Ig mutation hotspot than RGYW/WRCY We also found evidence that a DNA repair enzyme may play a role in modifying the sequence of hypermutation hotspots.
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