Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation.

Affinity maturation of the humoral immune response by somatic hypermutation is marked by a rapid and dramatic increase in affinity for the eliciting antigen. We suggest that the optimal mutation schedule is one in which periods of rapid mutation alternate with periods of mutation-free growth. The multicompartmental structure of the germinal center, together with re-entry of positively selected B cells back into the germinal center, will naturally implement such a schedule, thereby providing an anatomical basis for the efficiency of the germinal center reaction.