Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome

Rita Carsetti, Diletta Valentini, Valentina Marcellini, Marco Scarsella, Emiliano Marasco, Ferruccio Giustini, Andrea Bartuli, Alberto Villani, Alberto G. Ugazio

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)903-914
Number of pages12
JournalEuropean Journal of Immunology
Volume45
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • B cells
  • Down syndrome
  • IgM memory
  • Switched memory
  • TLR9
  • Vaccine

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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