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A reduction in B\u2010cell numbers has been reported, associated with moderate immunodeficiency and normal immunoglobulin levels. Here, we compared B\u2010cell populations of 19 children with DS with those in healthy age\u2010matched controls. We found that all steps of peripheral B\u2010cell development are altered in DS, with a more severe defect during the later stages of B\u2010cell development. Transitional and mature\u2010na\u00efve B\u2010cell numbers are reduced by 50% whereas switched memory B cells represent 10\u201315% of the numbers in age\u2010matched 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\u2010forming 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.<\/jats:p>","DOI":"10.1002\/eji.201445049","type":"journal-article","created":{"date-parts":[[2014,12,5]],"date-time":"2014-12-05T14:59:33Z","timestamp":1417791573000},"page":"903-914","source":"Crossref","is-referenced-by-count":77,"title":["Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome"],"prefix":"10.1002","volume":"45","author":[{"given":"Rita","family":"Carsetti","sequence":"first","affiliation":[{"name":"Immunology Unit Immunology and Pharmacotherapy Area Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"},{"name":"Diagnostic Immunology Unit Department of Laboratories Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Valentini","sequence":"additional","affiliation":[{"name":"Pediatric and Infectious Disease Unit Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Marcellini","sequence":"additional","affiliation":[{"name":"Immunology Unit Immunology and Pharmacotherapy Area Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Scarsella","sequence":"additional","affiliation":[{"name":"Immunology Unit Immunology and Pharmacotherapy Area Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Marasco","sequence":"additional","affiliation":[{"name":"Immunology Unit Immunology and Pharmacotherapy Area Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruccio","family":"Giustini","sequence":"additional","affiliation":[{"name":"Department of Laboratories Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bartuli","sequence":"additional","affiliation":[{"name":"Rare Disease and Medical Genetics Unit Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Villani","sequence":"additional","affiliation":[{"name":"Pediatric and Infectious Disease Unit Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto G.","family":"Ugazio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Bambino Ges\u00f9 Children's Hospital  IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2011.04335.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2010.05.007"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)05264-2"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(00)00435-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-200108000-00008"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-002-1078-6"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010101)98:1<70::AID-AJMG1002>3.0.CO;2-G"},{"key":"e_1_2_7_9_1","first-page":"186","article-title":"Increased incidence and prevalence of diabetes mellitus in Down's syndrome","volume":"77","author":"Goor J. 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