title: Defective B-cell memory in patients with Down syndrome.
abstract: BACKGROUND
  Patients with Down syndrome carry immunologic defects, as evidenced by the increased risks for autoimmune diseases, hematologic malignancies, and respiratory tract infections. Moreover, the low numbers of circulating B cells suggest impaired humoral immunity.
  
  
  OBJECTIVE
  We sought to study how immunodeficiency in patients with Down syndrome results from immunologic defects in the B-cell compartment.
  
  
  METHODS
  We studied blood B-cell subset composition, replication history, somatic hypermutation status, and class-switch recombination in 17 children with Down syndrome. Germinal centers and plasma cells were studied in tonsils from 4 additional children with Down syndrome.
  
  
  RESULTS
  Blood transitional B-cell numbers were normal, but naive mature and memory B-cell numbers were reduced despite slightly increased serum B cell-activating factor levels. Germinal centers and plasma cells in tonsils appeared normal, as were serum immunoglobulin levels. CD27(+)IgD(+)IgM(+) "natural effector" B cells showed reduced proliferation and somatic hypermutation levels, whereas these were normal in CD27(+)IgD(-) memory B cells. Furthermore, IgM(+) and IgA(+), but not IgG(+), memory B cells showed impaired molecular signs for antigen selection. The B-cell pattern was highly similar to that of patients with common variable immunodeficiency and a defect in B-cell activation and proliferation.
  
  
  CONCLUSIONS
  Children with Down syndrome seem capable of normal germinal center and plasma cell formation. Still, blood memory B-cell numbers were reduced and showed impaired molecular maturation of IgA and IgM, which are important for mucosal immunity. The observed molecular defects in circulating IgA and IgM B-cell memory could reflect impaired local responses, which underlie the increased susceptibility to respiratory tract infections of patients with Down syndrome.
authors.affiliation: Department of Pediatrics, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
authors.forename: Ruud H J
authors.initials: RHJ
authors.lastname: Verstegen
authors.affiliation: Department of Pediatric Infectious Disease and Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Gertjan J
authors.initials: GJ
authors.lastname: Driessen
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Sophinus J W
authors.initials: SJW
authors.lastname: Bartol
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Carel J M
authors.initials: CJM
authors.lastname: van Noesel
authors.affiliation: Bioceros B.V., Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jacques J M
authors.initials: JJM
authors.lastname: van Dongen
authors.affiliation: Department of Pediatrics, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands. Electronic address: e.d.vries@jbz.nl.
authors.forename: Esther
authors.initials: E
authors.lastname: de Vries
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Menno C
authors.initials: MC
authors.lastname: van Zelm
mesh_terms: D000293:Adolescent; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000276:immunology; D004314:Down Syndrome / Q000276:immunology*; D005260:Female; D018858:Germinal Center; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008297:Male; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M
keywords: B cell; Down syndrome; IgA; IgM; antibody; common variable immunodeficiency; plasma cell; selection; somatic hypermutation