In the humoral arm of the immune system, the memory response is not only more quickly elicited and of greater magnitude than the primary response, but it is also different in quality. In the recall response to antigen, the antibodies produced are of higher affinity and of different isotype (typically immunoglobulin G rather than immunoglobulin M). This maturation rests on the antigen dependence of B–cell maturation and is effected by programmed genetic modifications of the immunoglobulin gene loci. Here we consider how the B–cell response to antigen depends on the affinity of the antigen–receptor interaction. We also compare and draw parallels between the two processes, which underpin the generation of secondaryresponse antibodies: V gene somatic hypermutation and immunoglobulin heavy–chain class switching.