Location and length distribution of somatic hypermutation-associated DNA insertions and deletions reveals regions of antibody structural plasticity.

Briney, B S; Willis, J R; Crowe, J E

Following the initial diversity generated by V(D)J recombination, somatic hypermutation is the principal mechanism for producing further antibody repertoire diversity in antigen-experienced B cells. While somatic hypermutation typically results in single-nucleotide substitutions, the infrequent incorporation of genetic insertions and deletions has also been associated with the somatic hypermutation process. We used high-throughput antibody sequencing to determine the sequence of thousands of antibody genes containing somatic hypermutation-associated insertions and deletions (SHA indels), which revealed significant differences between the location of SHA indels and somatic mutations. Further, we identified a cluster of insertions and deletions in the antibody framework 3 region, which corresponds to the hypervariable region 4 (HV4) in T-cell receptors. We propose that this HV4-like region, identified by SHA indel analysis, represents a region of under-appreciated affinity maturation potential. Finally, through the analysis of both location and length distribution of SHA indels, we have determined regions of structural plasticity within the antibody protein.

DNA; IMMUNOGLOBULINS; PROTEIN structure; GENE conversion; BIODIVERSITY; NUCLEOTIDE sequence; B cells; GENETIC mutation

Genes & Immunity, 2012, Vol 13, Issue 7, p523

1466-4879

Academic Journal

10.1038/gene.2012.28