Affinity maturation and class switching.

Affinity maturation and class switching of antibodies are temporally, but not mechanistically, related processes. The basis of affinity maturation is the selection, in the germinal centers, of antibodies that bind the antigen better. Early in an immune response, the selection is from the primary repertoire; later, it is from mutants generated by hypermutation at the immunoglobulin loci. Recently, the door has been opened for the study of the molecular mechanism of hypermutation, which is expected to make a major contribution to general biology. Class switching has been studied in the past for its obvious clinical importance, but also at the basic level of DNA recombination. Progress in understanding class switching has been trailing the progress made in V(D)J recombination, but new in vitro systems and gene-targeted mice are closing the gap.