Somatic mutation leads to efficient affinity maturation when centrocytes recycle back to centroblasts.

M Oprea, AS Perelson - Journal of immunology (Baltimore, Md …, 1997 - journals.aai.org
M Oprea, AS Perelson
Journal of immunology (Baltimore, Md.: 1950), 1997journals.aai.org
Although most mutations are deleterious, an interplay between somatic mutation and
selection within germinal centers (GC) results in rapid generation of high affinity memory B
cells. How high affinity 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 Ag-selected centrocytes back into …
Abstract
Although most mutations are deleterious, an interplay between somatic mutation and selection within germinal centers (GC) results in rapid generation of high affinity memory B cells. How high affinity 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 Ag-selected centrocytes back into centroblasts can lead to efficient affinity 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 GC dissociation, followed by the release of centrocytes into the periphery, is advantageous for generating high affinity memory.
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