DEFINING SUBSETS OF NAIVE AND MEMORY B-CELLS BASED ON THE ABILITY OF THEIR PROGENY TO SOMATICALLY MUTATE IN-VITRO

The increased affinity of memory antibody responses is due largely to the generation and selection of memory a cells that accumulate somatic mutations after initial antigenic stimulation. Further affinity matur ation and mutation also accompany subsequent immunizations. Previous s tudies have suggested that, like primary antibody-forming eel (AFC) cl ones, secondary AFC do not accumulate further mutations and, therefore , the origins of progressive affinity maturation remain controversial, Here, we report the generation of somatically mutated memory B cell c lones in vitro. Our findings confirm the existence of a naive B cell s ubset whose progeny, rather than generating AFC, somatically mutate an d respond to subsequent antigenic stimulation. Interestingly, upon sti mulation, a subset of memory B cells also generates antigen-responsive cells that accumulate further somatic mutations.