Antigen-specific B cell memory: Expression and replenishment of a novel B220(-) memory B cell compartment

The mechanisms that regulate B cell memory and the rapid recall response to antigen remain poorly defined. This study focuses on the rapid expression of B cell memory upon antigen recall in vivo, and the replenishment of quie scent B cell memory that follows. Based oil expression of CD138 and B220, w e reveal a unique and major subtype of antigen-specific memory B cells (B22 0(-)CD138(-)) that are distinct from antibody-secreting B cells (D220(+/-)C D138(+)) and B220(+)CD138(-) memory B cells. These nonsecreting somatically mutated B220(-) memory responders rapidly dominate the splenic response an d comprise >95% of antigen-specific memory B cells that migrate to thr bone marrow. By day 42 after recall, the predominant quiescent memory B cell po pulation in the spleen (75-85%) and the bone marrow (>95%) expresses the B2 20(-) phenotype. Upon adoptive transfer, B220(-) memory B cells proliferate to a lesser degree but produce greater amounts of antibody than their B220 (+) counterparts, The pattern of cellular differentiation after transfer in dicates that B220(-) memory B cells act as stable self-replenishing interme diates that arise from B220(+) memory B cells and produce antibody-secretin g cells oil rechallenge with antigen. Cell surface phenotype and Ig isotype expression divide the B220(-) compartment into two main subsets with disti nct patterns of integrin and coreceptor expression. Thus, we identify new c ellular components of B cell memory and propose a model for long-term prote ctive immunity that is regulated by a complex balance of committed memory B cells with subspecialized immune function.