The Interplay between CD27dull and CD27bright B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory

Abstract

Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27^dull and CD27^bright MBCs, 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 CD27^dull and CD27^bright MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27^dull into the CD27^bright MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27^dull MBCs transit to the more differentiated CD27^bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27^dull clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27^dull MBCs that expand and differentiate in response to change.