The efficiency of affinity maturation can only be explained by multiple rounds of mutation-selection-expansion of lymphocytes

The germinal center reaction is generally described as a one-pass process, with B cells coming into the germinal center, undergoing division and somatic mutation in one compartment, then moving into another compartment for selection, and finally leaving the germinal center. There have been a number of studies showing that a large number of high affinity mutants can be produced more efficiently if cells were to cycle between the selection compartment and the reproduction compartment. In chapter I showed quantitatively that the one-pass scenario is incompatible with the observed efficiency of affinity maturation. I also showed that the decay of the selective agent (antigen) reduces the efficiency of amplification of high-affinity cells from linear to logarithmic in their selective advantage. This gives even more theoretical support to the recycling hypothesis. It also provides useful insights into processes in which selection is due to an agent that decays in time.