title: Human B-cell memory is shaped by age- and tissue-specific T-independent and GC-dependent events.
abstract: Switched and IgM memory B cells execute different and noninterchangeable functions. We studied memory B cells in children of different ages, in peripheral blood and spleen and compared them with those of children born asplenic or unable to build germinal centers. We show that, whereas switched memory B cells are mostly generated in the germinal centers at all ages, IgM memory B cells can be distinct in three types with different developmental history. Innate IgM memory B cells, the largest pool in infants, are generated in the spleen by a germinal center-independent mechanism. With age, if the spleen is present and germinal centers are functional, innate IgM memory B cells are remodelled and accumulate somatic mutations. The third type of IgM memory B cell is a by-product of the germinal center reaction. Our data suggest that the B-cell memory developmental program is implemented during the first 5-6 years of life.
authors.affiliation: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino, Gesù IRCSS, Roma, Italy.
authors.forename: Alaitz
authors.initials: A
authors.lastname: Aranburu
authors.affiliation: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino, Gesù IRCSS, Roma, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Piano Mortari
authors.affiliation: Medical and Surgical Department of Pediatric Cardiology, Bambino Gesù Children Hospital, Rome.
authors.forename: Anwar
authors.initials: A
authors.lastname: Baban
authors.affiliation: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino, Gesù IRCSS, Roma, Italy.
authors.forename: Ezio
authors.initials: E
authors.lastname: Giorda
authors.affiliation: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino, Gesù IRCSS, Roma, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Cascioli
authors.affiliation: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino, Gesù IRCSS, Roma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marcellini
authors.affiliation: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino, Gesù IRCSS, Roma, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Scarsella
authors.affiliation: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino, Gesù IRCSS, Roma, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ceccarelli
authors.affiliation: Core Facilities, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Corbelli
authors.affiliation: Medical and Surgical Department of Pediatric Cardiology, Bambino Gesù Children Hospital, Rome.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Cantarutti
authors.affiliation: Division of Pathology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: De Vito
authors.affiliation: Pediatric General and Thoracic Surgery Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Inserra
authors.affiliation: Department of Pediatrics, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Nicolosi
authors.affiliation: Department of Pediatrics, University of Brescia, Brescia, Italy.
authors.forename: Arnalda
authors.initials: A
authors.lastname: Lanfranchi
authors.affiliation: Department of Pediatrics, University of Brescia, Brescia, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Porta
authors.affiliation: DPUO, University Department of Pediatrics, Bambino Gesù Children Hospital and University of Tor Vergata School of Medicine, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cancrini
authors.affiliation: DPUO, University Department of Pediatrics, Bambino Gesù Children Hospital and University of Tor Vergata School of Medicine, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
authors.affiliation: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino, Gesù IRCSS, Roma, Italy.|Diagnostic Immunology Unit, Department of Oncohematology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
mesh_terms: D000293:Adolescent; D000375:Aging / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D017578:Immunoglobulin Class Switching; D007075:Immunoglobulin M / Q000378:metabolism; D007156:Immunologic Memory; D007223:Infant; D008297:Male; D009928:Organ Specificity; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007075:Immunoglobulin M
keywords: Antibodies; B cell development; B cells; Immunoglobulins; Innate immunity