Discriminating intrinsic and antigen-selected mutational hotspots in immunoglobulin V genes

Studies of the antibody hypermutation mechanism have revealed that it is not a random process but exhibits characteristic nucleotide substitution preferences. Here, Alexander Betz and colleagues show that these innate nucleotide substitution preferences can be used to examine databases of antigen-selected V gene sequences and thereby distinguish intrinsic from antigen-selected hotspots. This analysis reveals intrinsic mutational hotspots in both VH and VL genes, reflecting innate features of the hypermutation machinery which may give clues to the enzymatic mechanism.