The Interplay between CD27(dull) and CD27(brig)(ht) B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory

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Authors

GRIMSHOLM O. MORTARI E.P. DAVYDOV Alexey Nikolayevich SHUGAY M. OBRAZTSOVA A.S. BOCCI C. MARASCO E. MARCELLINI V. ARANBURU A. FARRONI C. SILVESTRIS D.A. CRISTOFOLETTI C. GIORDA E. SCARSELLA M. CASCIOLI S. BARRESI S. LOUGARIS V. PLEBANI A. CANCRINI C. FINOCCHI A. MOSCHESE V. VALENTINI D. VALLONE C. SIGNORE F. DE VINCENTIIS G. ZAFFINA S. RUSSO G. GALLO A. LOCATELLI F. TOZZI A.E. TARTAGLIA M. CHUDAKOV Dmitriy CARSETTI R.

Year of publication 2020
Type Article in Periodical
Magazine / Source Cell Reports
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://www.sciencedirect.com/science/article/pii/S2211124720301765?via%3Dihub
Doi http://dx.doi.org/10.1016/j.celrep.2020.02.022
Keywords HYPER-IGM SYNDROME; NEUTRALIZING ANTIBODIES; SOMATIC HYPERMUTATION; INFECTIONS; ACTIVATION; SUBSETS; DIFFERENTIATION; PROLIFERATION; COMPARTMENT; DEFICIENCY
Description 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(du)(ll) and CD27(bright) MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27(du)(ll) into the CD27(bright) MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27(du)(ll) 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(du)(ll) clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27(du)(ll) MBCs that expand and differentiate in response to change.
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