title: Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome.
abstract: Children with Down syndrome (DS) have increased susceptibility to infections and a high frequency of leukemia and autoimmune disorders, suggesting that immunodeficiency and immune dysfunction are integral parts of the syndrome. A reduction in B-cell numbers has been reported, associated with moderate immunodeficiency and normal immunoglobulin levels. Here, we compared B-cell populations of 19 children with DS with those in healthy age-matched controls. We found that all steps of peripheral B-cell development are altered in DS, with a more severe defect during the later stages of B-cell development. Transitional and mature-naïve B-cell numbers are reduced by 50% whereas switched memory B cells represent 10-15% of the numbers in age-matched controls. Serum IgM levels were slightly reduced, but all other immunoglobulin isotypes were in the normal range. The frequency of switched memory B cells specific for vaccine antigens was significantly lower in affected children than in their equivalently vaccinated siblings. In vitro switched memory B cells of patients with DS have an increased ability to differentiate into antibody-forming cells in response to TLR9 signals. Tailored vaccination schedules increasing the number of switched memory B cells may improve protection and reduce the risk of death from infection in DS.
authors.affiliation: Immunology Unit, Immunology and Pharmacotherapy Area, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Diagnostic Immunology Unit, Department of Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
authors.forename: Diletta
authors.initials: D
authors.lastname: Valentini
authors.forename: Valentina
authors.initials: V
authors.lastname: Marcellini
authors.forename: Marco
authors.initials: M
authors.lastname: Scarsella
authors.forename: Emiliano
authors.initials: E
authors.lastname: Marasco
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Giustini
authors.forename: Andrea
authors.initials: A
authors.lastname: Bartuli
authors.forename: Alberto
authors.initials: A
authors.lastname: Villani
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Ugazio
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D002648:Child; D004314:Down Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D007156:Immunologic Memory; D008297:Male; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D014612:Vaccines / Q000627:therapeutic use
chemical_list: D007075:Immunoglobulin M; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D014612:Vaccines
keywords: B cells; Down syndrome; IgM memory; Switched memory; TLR9; Vaccine