Somatic hypermutation shapes the antibody repertoire of memory B cells in humans

High-affinity antibodies produced by memory B cells differ from antibodies produced in naive B cells in two respects. First, many of these antibodies show somatic hypermutation, and second, the repertoire of antibodies expres sed in memory responses is highly selected. To determine whether somatic hy permutation is responsible for the shift in the antibody repertoire during affinity maturation, we analyzed the immunoglobulin lambda light chain (Ig lambda) repertoire expressed by naive and antigen-selected memory B cells i n humans. We found that the Ig lambda repertoire differs between naive and memory B cells and that this shift in the repertoire does not occur in the absence of somatic hypermutation in patients lacking activation-induced cyt idine deaminase (AID). Our work suggests that somatic hypermutation makes a significant contribution to shaping the antigen-selected antibody repertoi re in humans.