Cell Reports (Mar 2020)
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 Finocchi,
- Viviana 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
Affiliations
- Ola Grimsholm
- B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy; Department of Rheumatology and Inflammation Research, University of Gothenburg, Box 480, 405 30 Gothenburg, Sweden
- Eva Piano Mortari
- B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy
- Alexey N. Davydov
- Central European Institute of Technology, 625 00 Brno, Czech Republic
- Mikhail Shugay
- Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia; Institute of Translational Medicine, Pirogov Russian National Research Medical University, 117997 Moscow, Russia; Center of Life Sciences, Skolkovo Institute of Science and Technology, 101000 Moscow, Russia
- Anna S. Obraztsova
- Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia; Center of Life Sciences, Skolkovo Institute of Science and Technology, 101000 Moscow, Russia
- Chiara Bocci
- B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy
- Emiliano Marasco
- Division of Rheumatology, Bambino Gesù Children’s Hospital IRCCS, 00146 Roma, Italy
- Valentina Marcellini
- B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy
- Alaitz Aranburu
- Department of Rheumatology and Inflammation Research, University of Gothenburg, Box 480, 405 30 Gothenburg, Sweden
- Chiara Farroni
- B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy
- Domenico Alessandro Silvestris
- Oncohaematology Department, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy
- Cristina Cristofoletti
- Istituto Dermopatico dell’Immacolata (IDI), IRCCS, 00167 Rome, Italy
- Ezio Giorda
- B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy
- Marco Scarsella
- B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy
- Simona Cascioli
- B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy
- Sabina Barresi
- Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, 00146 Rome, Italy
- Vassilios Lougaris
- Department of Experimental and Clinical Sciences, University of Brescia, 25121 Brescia, Italy
- Alessandro Plebani
- DPUO, Division of Immuno-Infectivology, University Department of Pediatrics, 00146 Bambino Gesù Children’s Hospital, Rome, Italy
- Caterina Cancrini
- DPUO, Division of Immuno-Infectivology, University Department of Pediatrics, 00146 Bambino Gesù Children’s Hospital, Rome, Italy; School of Medicine, University of Tor Vergata, 00133 Rome, Italy
- Andrea Finocchi
- DPUO, Division of Immuno-Infectivology, University Department of Pediatrics, 00146 Bambino Gesù Children’s Hospital, Rome, Italy; School of Medicine, University of Tor Vergata, 00133 Rome, Italy
- Viviana Moschese
- Pediatric Immunology Unit, Policlinico Tor Vergata, University of Rome Tor Vergata, 00133 Rome, Italy
- Diletta Valentini
- Pediatric and Infectious Disease Unit, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
- Cristina Vallone
- Department of Obstetrics and Gynaecology, Misericordia Hospital Grosseto, Usl Toscana Sud-est, 58100 Grosseto, Italy
- Fabrizio Signore
- Department of Obstetrics and Gynaecology, Misericordia Hospital Grosseto, Usl Toscana Sud-est, 58100 Grosseto, Italy
- Giovanni de Vincentiis
- Otorhinolaryngology Unit, Bambino Gesù Children’s Hospital, IRCSS, 00146 Rome, Italy
- Salvatore Zaffina
- Occupational Medicine/Health Technology Assessment and Safety Research Unit, Clinical-Technological Innovations Research Area, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
- Giandomenico Russo
- Istituto Dermopatico dell’Immacolata (IDI), IRCCS, 00167 Rome, Italy
- Angela Gallo
- Oncohaematology Department, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy
- Franco Locatelli
- Oncohaematology Department, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy; Department of Pediatrics, Sapienza, University of Rome, 00161 Rome, Italy
- Alberto E. Tozzi
- Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children’s Hospital, IRCSS, 00146 Rome, Italy
- Marco Tartaglia
- Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, 00146 Rome, Italy
- Dmitriy M. Chudakov
- Central European Institute of Technology, 625 00 Brno, Czech Republic; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia; Institute of Translational Medicine, Pirogov Russian National Research Medical University, 117997 Moscow, Russia; Center of Life Sciences, Skolkovo Institute of Science and Technology, 101000 Moscow, Russia
- Rita Carsetti
- B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital IRCCS, 00146 Rome, Italy; Diagnostic Immunology Unit, Department of Laboratories, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; Corresponding author
- Journal volume & issue
-
Vol. 30,
no. 9
pp. 2963 – 2977.e6
Abstract
Summary: 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. : Grimsholm et al. show that CD27dull and CD27bright represent sequential MBC developmental stages. T cell- and germinal center (GC)-independent CD27dull MBCs are the plastic source of strongly selected and GC-dependent CD27bright MBCs. CD27dull MBCs, able to expand and differentiate in response to change, ensure stability and flexibility of human B cell memory. Keywords: memory B cells, pregnancy, immunological memory, CD27, VH repertoire, immunodeficiency, aging, spleen, vaccine, germinal center
