The Interplay between CD27dulland CD27brightB Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory

Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dulland CD27brightMBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27dulland CD27brightMBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27dullinto the CD27brightMBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27dullMBCs transit to the more differentiated CD27brightstage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27dullclones. Thus, the stability and flexibility of human B cell memory is ensured by CD27dullMBCs that expand and differentiate in response to change.