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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Thiel, J; Kimmig, L; Salzer, U; Grudzien, M; Lebrecht, D; Hagena, T; Draeger, R; Voelxen, N; Völxen, N; Bergbreiter, A; Jennings, S; Gutenberger, S; Aichem, A; Illges, H; Hannan, JP; Kienzler, AK; Rizzi, M; Eibel, H; Peter, HH; Warnatz, K; Grimbacher, B; Rump, JA; Schlesier, M.
Genetic CD21 deficiency is associated with hypogammaglobulinemia.
J Allergy Clin Immunol. 2012; 129(3):801-810.e6
Doi: 10.1016/j.jaci.2011.09.027
(- Case Report)
Web of Science
PubMed
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- Leading authors Med Uni Graz
- Thiel Jens
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult - administration & dosage
- Agammaglobulinemia - complications, diagnosis, genetics, immunology
- Antigen-Antibody Complex - metabolism
- B-Lymphocytes - immunology, metabolism, pathology
- Calcium Signaling - genetics
- Complement C3d - metabolism
- DNA Mutational Analysis - administration & dosage
- HEK293 Cells - administration & dosage
- Humans - administration & dosage
- Immunity, Humoral - genetics
- Immunologic Memory - genetics
- Infections - diagnosis, etiology, genetics, immunology
- Male - administration & dosage
- Protein Binding - genetics
- Receptors, Complement 3d - genetics, immunology, metabolism
- Sequence Deletion - genetics
- Transgenes - genetics
- Viral Matrix Proteins - metabolism
- Find related publications in this database (Keywords)
- CD21
- complement receptor
- hypogammaglobulinemia
- common variable immunodeficiency
- B lymphocyte