Evolution in miniature: selection, survival and distribution of antigen reactive cells in the germinal centre

Abstract

Productive immune responses to T-cell-dependent antigens ultimately generate two long-lived compartments: memory B cells and bone marrow-resident plasma cells, which both arise from within germinal centres. The ability of a B-cell clone to populate these effector compartments requires its descendents to outcompete those of other clones participating in the response. Selection occurs at several stages of the response and the criteria differ at these different stages. While affinity predominates as the key, underlying driving force of selection, there is a distinction made at the point at which germinal centre cells initiate entry into the plasma cell and memory B-cell compartments. Becoming a plasma cell requires high affinity and cannot be subverted by blocking cell death, while becoming a memory B cell is dependent on survival alone. While such survival is typically mediated by affinity within the GC, the distinction has important mechanistic implications.