Somatic Mutation Leads to Eecient Aanity Maturation When Centrocytes Recycle Back to Centroblasts

Though most mutations are deleterious, an interplay between somatic mutation and selection within germinal centers (GC) results in rapid generation of high a nity memory B cells. How high a nity B cells with large numbers of mutations are generated and preserved, within GC containing at their peak only a few thousand cells, has been puzzling. We have developed a model of somatic mutation and B cell expansion within a GC that resolves this puzzle. We show that the frequent recycling of antigen-selected centrocytes back into centroblasts can lead to e cient a nity maturation. Memory cells are generated in large numbers even when most of the selected centrocytes recycle back into centroblasts. Our model suggests that a germinal center reaction in which the output of cells is low up to the point of germinal center dissociation, followed by the release of centrocytes into the periphery, is advantageous for generating high a nity memory. 2