Antibody Affinity Maturation by Random Mutagenesis

The immune response to an antigen can be considered to occur in two stages. In the initial stage, low-affinity antibodies are generated from an existing pool of the B-cell repertoires available at the time of immunization. In the second stage, which is driven by antigen stimulation, high-affinity antibodies are produced as a result of affinity maturation, starting with the light- and heavy-chain variable region (V_L and V_H ) genes selected in the primary response. The mechanism for affinity maturation consists of somatic hypermutation of V-region genes followed by clonal selection of B-cells that produce antibodies of the highest affinity. Recent advances in phage-displayed antibody technology have enabled the affinity maturation process to be mimicked in vitro to improve the antigen-binding affinity and even alter the binding specificity of recombinant antibodies (1 –6 ).