Somatic insertions and deletions shape the human antibody repertoire.
We have sequenced the heavy and light chain genes from 365 IgG(+) B cells and found that 24 (6.5 %) contain somatically introduced insertions or deletions. These insertions and deletions are clustered at "hot-spots" in the antigen-binding site and frequently result in the creation of new combinations of canonical loop structures or entirely new loops that are not present in the human germline repertoire, but are similar to those seen in other species. Somatic insertion and deletion therefore provides a further mechanism for introducing structural diversity into antibodies in addition to somatic point mutation and receptor editing, which have small (single amino acid changes) and large (chain replacement) impacts on structural diversity, respectively.
de Wildt
R M
RM
MRC Centre for Protein Engineering and MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK. rdw@mrc-lmb.cam.ac.uk
van Venrooij
W J
WJ
Winter
G
G
Hoet
R M
RM
Tomlinson
I M
IM
D000328:Adult; D000595:Amino Acid Sequence; D000916:Antibody Diversity / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D017384:Sequence Deletion
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region