ABSTRACT
In conjunction with the accumulating mutations, an increase in the average affinity of antibody for the stimulating antigen is found. Many intriguing questions exist about the detailed mechanisms of affinity maturation. The modeling approach illustrates the way in which imagery evoked by the term "rugged landscape" can be translated into quantitative predictions about the affinity maturation process. The increase of affinity has been studied experimentally in more detail by making hybridomas from antibody-secreting cells, measuring the affinity of the resulting monoclonal antibody, and sequencing the immunoglobulin messengerRNA. A natural measure of fitness is the antibody affinity for the immunizing antigen. The halting in affinity improvement is predicted to occur due to trapping at a local optimum or near a local optimum where improvement mutations become rare. Affinity maturation by somatic mutation seems an ideal system in which nature is allowing to examine in detail the relationships between antibody sequence, antibody structure, and antibody function.
