Genetic CD21 deficiency is associated with hypogammaglobulinemia.
J Allergy Clin Immunol
; 129(3): 801-810.e6, 2012 Mar.
Article
en En
| MEDLINE
| ID: mdl-22035880
ABSTRACT
BACKGROUND:
Complement receptor 2 (CR2/CD21) is part of the B-cell coreceptor and expressed by mature B cells and follicular dendritic cells. CD21 is a receptor for C3d-opsonized immune complexes and enhances antigen-specific B-cell responses.OBJECTIVE:
Genetic inactivation of the murine CR2 locus results in impaired humoral immune responses. Here we report the first case of a genetic CD21 deficiency in human subjects.METHODS:
CD21 protein expression was analyzed by means of flow cytometry and Western blotting. CD21 transcripts were quantified by using real-time PCR. The CD21 gene was sequenced. Wild-type and mutant CD21 cDNA expression was studied after transfection of 293T cells. Binding of EBV-gp350 or C3d-containing immune complexes and induction of calcium flux in CD21-deficient B cells were analyzed by means of flow cytometry. Antibody responses to protein and polysaccharide vaccines were measured.RESULTS:
A 28-year-old man presented with recurrent infections, reduced class-switched memory B cells, and hypogammaglobulinemia. CD21 receptor expression was undetectable. Binding of C3d-containing immune complexes and EBV-gp350 to B cells was severely reduced. Sequence analysis revealed a compound heterozygous deleterious mutation in the CD21 gene. Functional studies with anti-immunoglobulin- and C3d-containing immune complexes showed a complete loss of costimulatory activity of C3d in enhancing suboptimal B-cell receptor stimulation. Vaccination responses to protein antigens were normal, but the response to pneumococcal polysaccharide vaccination was moderately impaired.CONCLUSIONS:
Genetic CD21 deficiency adds to the molecular defects observed in human subjects with hypogammaglobulinemia.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Receptores de Complemento 3d
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Agammaglobulinemia
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Infecciones
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Risk_factors_studies
Límite:
Adult
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Humans
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Male
Idioma:
En
Año:
2012
Tipo del documento:
Article