Is rapid proliferation in B centroblasts linked to somatic mutation in memory B cell clones?

Abstract

Antigen-reactive B cells accumulate mutations in the variable (v) regions of their immunoglobulin genes during certain phases of T cell-dependent (TD) antibody responses. This is associated with a rise in the affinity of specific antibody. The time when somatic mutations are accumulating seems to coincide with the presence of germinal centres. This has led to the suggestion that a mechanism leading to a high rate of base pair substitution in immunoglobulin v region genes might operate in centroblasts in germinal centres. The rate of accumulation of mutations in v region genes is likely to relate to the number of specific B cells in cycle and their rate of cell division. The present report provides evidence pointing to centroblasts having a remarkably short cell cycle time of some 6 to 7 hours. This rapid rate of proliferation may explain the clonal expansion which occurs in the early phase of TD antibody responses and the efficiency with which high affinity mutants are subsequently selected.