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

Ola Grimsholm, Eva Piano Mortari, Alexey N Davydov, Mikhail Shugay, Anna S Obraztsova, Chiara Bocci, Emiliano Marasco, Valentina Marcellini, Alaitz Aranburu, Chiara Farroni, Domenico Alessandro Silvestris, Cristina Cristofoletti, Ezio Giorda, Marco Scarsella, Simona Cascioli, Sabina Barresi, Vassilios Lougaris, Alessandro Plebani, Caterina Cancrini, Andrea FinocchiViviana Moschese, Diletta Valentini, Cristina Vallone, Fabrizio Signore, Giovanni de Vincentiis, Salvatore Zaffina, Giandomenico Russo, Angela Gallo, Franco Locatelli, Alberto E Tozzi, Marco Tartaglia, Dmitriy M Chudakov, Rita Carsetti

Research output: Contribution to journalArticlepeer-review

Abstract

Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright 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 CD27dull and CD27bright MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27dull into the CD27bright MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27dull MBCs transit to the more differentiated CD27bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27dull clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27dull MBCs that expand and differentiate in response to change.

Original languageEnglish
Pages (from-to)2963-2977.e6
JournalCell Reports
Volume30
Issue number9
DOIs
Publication statusPublished - Mar 3 2020

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