In the course of the humoral immune response, the average affinity of the antibodies produced increases as much as 100 to 10,000 fold. This affinity maturation is the result of antigen selection and somatic hypermutation of high-affinity clones. Somatic hypermutation occurs in lymphocytes undergoing expansion in the dark zones. Most of the resulting centrocytes do not bear a high affinity receptor for the Ag and die. Centrocytes with high affinity receptors are positively selected.
Models suggest that multiple rounds of selection and somatic mutation take place.
The affinity of the Ab secreted by a plasma cell corresponds to that of the mIg of the B cells from which it was derived. As Ag levels decline over time following immunization, only those B cells possessing high-affinity mIg are able to bind sufficient antigen to be activated and clonally expanded. Similarly, if the initial Ag dose is low, only high-affinity B cells are activated. These patients also fail to develop germinal centers and class switch. The cytokines secreted by the TH cells help determine the isotype produced.