Defective B-cell memory in patients with Down syndrome
Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved..
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.
CONCLUSION: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:134 |
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| Enthalten in: |
The Journal of allergy and clinical immunology - 134(2014), 6 vom: 27. Dez., Seite 1346-1353.e9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Verstegen, Ruud H J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.02.2015 Date Revised 15.09.2017 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaci.2014.07.015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM241322081 |
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| 100 | 1 | |a Verstegen, Ruud H J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Defective B-cell memory in patients with Down syndrome |
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| 500 | |a Date Revised 15.09.2017 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a OBJECTIVE: We sought to study how immunodeficiency in patients with Down syndrome results from immunologic defects in the B-cell compartment | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a B cell | |
| 650 | 4 | |a Down syndrome | |
| 650 | 4 | |a IgA | |
| 650 | 4 | |a IgM | |
| 650 | 4 | |a antibody | |
| 650 | 4 | |a common variable immunodeficiency | |
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| 650 | 4 | |a somatic hypermutation | |
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| 700 | 1 | |a Driessen, Gertjan J |e verfasserin |4 aut | |
| 700 | 1 | |a Bartol, Sophinus J W |e verfasserin |4 aut | |
| 700 | 1 | |a van Noesel, Carel J M |e verfasserin |4 aut | |
| 700 | 1 | |a Boon, Louis |e verfasserin |4 aut | |
| 700 | 1 | |a van der Burg, Mirjam |e verfasserin |4 aut | |
| 700 | 1 | |a van Dongen, Jacques J M |e verfasserin |4 aut | |
| 700 | 1 | |a de Vries, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a van Zelm, Menno C |e verfasserin |4 aut | |
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