The Interplay between CD27 dull and CD27 bright B 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, 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.
Competing Interests: Declaration of Interests The authors declare no competing interests.
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