Maintenance of B-cell memory by long-lived cells generated from proliferating precursors

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Abstract
A BASIC feature of T-cell dependent antibody responses is the generation of memory: on a second contact with an antigen a secondary response is produced in which somatically mutated antibodies with increased affinity are synthesized1. Memory can persist for long periods of time. This has classically been ascribed to the generation of long-lived memory B cells2,3. However, it is also possible that persisting antigen, on which memory may depend4, maintains a population of cycling memory cells under continuous selection5 or continuously recruits newly generated B cells into the memory B-cell compartment6. To discriminate between these mechanisms we have now directly analysed the proliferative activity in the memory B-cell compartment of the mouse by measuring bromodeoxyuridine incorporation in vivo. We show that after an initial phase of extensive proliferation after primary immunization, memory cells can persist in the organism for extended periods of time in the absence of cell division.