Journal
CELL REPORTS
Volume 30, Issue 9, Pages 2963-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.02.022
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Funding
- Italian Ministry of Health [RF201302358960]
- Associazione Arcobaleno
- EMBO
- C.M. Lerici Foundation
- Royal Society of Arts and Sciences in Gothenburg
- Ministry of Education, Youth and Sports of the Czech Republic [CEITEC 2020 LQ1601]
- Russian Science Foundation [19-14-00317]
- Russian Science Foundation [19-14-00317] Funding Source: Russian Science Foundation
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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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