title: Expression of immunoglobulin receptors with distinctive features indicating antigen selection by marginal zone B cells from human spleen.
abstract: Marginal zone (MZ) B cells, identified as surface (s)IgM(high)sIgD(low)CD23(low/-)CD21(+)CD38(-) B cells, were purified from human spleens, and the features of their V(D)J gene rearrangements were investigated and compared with those of germinal center (GC), follicular mantle (FM) and switched memory (SM) B cells. Most MZ B cells were CD27(+) and exhibited somatic hypermutations (SHM), although to a lower extent than SM B cells. Moreover, among MZ B-cell rearrangements, recurrent sequences were observed, some of which displayed intraclonal diversification. The same diversifying sequences were detected in very low numbers in GC and FM B cells and only when a highly sensitive, gene-specific polymerase chain reaction was used. This result indicates that MZ B cells could expand and diversify in situ and also suggested the presence of a number of activation-induced cytidine deaminase (AID)-expressing B cells in the MZ. The notion of antigen-driven expansion/selection in situ is further supported by the VH CDR3 features of MZ B cells with highly conserved amino acids at specific positions and by the finding of shared ("stereotyped") sequences in two different spleens. Collectively, the data are consistent with the notion that MZ B cells are a special subset selected by in situ antigenic stimuli.
authors.affiliation: Direzione Scientifica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-IST, Genoa, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Division of Molecular Diagnostics, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.affiliation: Division of Pathology, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Reverberi
authors.affiliation: Department Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bruno
authors.affiliation: Department Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ghiotto
authors.affiliation: Department Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Claudya
authors.initials: C
authors.lastname: Tenca
authors.affiliation: Institute of Agrobiotechnology, Center for Research and Technology Hellas, Thessaloniki, Greece.|Hematology Department and Hematopoietic Cell Transplantation (HCT) Unit, G. Papanicolau Hospital, Thessaloniki, Greece.
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.affiliation: Institute of Agrobiotechnology, Center for Research and Technology Hellas, Thessaloniki, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Hadzidimitriou
authors.affiliation: Direzione Scientifica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-IST, Genoa, Italy.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ceccarelli
authors.affiliation: Division of Pathology, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Salvi
authors.affiliation: Division of Pathology, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Boccardo
authors.affiliation: Division of Epidemiology and Statistic, IRCCS Istituto G. Gaslini, Genoa, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Calevo
authors.affiliation: Department Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Amleto
authors.initials: A
authors.lastname: De Santanna
authors.affiliation: Division of Pathology, IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.affiliation: Department Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Fais
authors.affiliation: Direzione Scientifica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-IST, Genoa, Italy.
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015322:Gene Rearrangement, B-Lymphocyte; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D017422:Sequence Analysis, DNA; D027041:Somatic Hypermutation, Immunoglobulin; D013154:Spleen / Q000166:cytology* / Q000276:immunology