Genetic CD21 deficiency is associated with hypogammaglobulinemia - 01/03/12
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, Lucas Kimmig, MD a, , Ulrich Salzer, MD a, b, , Magdalena Grudzien, PhD a, Dirk Lebrecht, PhD a, Tina Hagena a, Ruth Draeger a, Nadine Völxen, MSc a, b, Astrid Bergbreiter, MSc a, b, Stephanie Jennings, PhD a, b, Sylvia Gutenberger a, b, Annette Aichem, PhD c, Harald Illges, PhD d, Jonathan P. Hannan, PhD e, Anne-Kathrin Kienzler, MSc a, b, f, Marta Rizzi, MD, PhD a, b, f, Hermann Eibel, PhD a, b, f, Hans-Hartmut Peter, MD a, b, Klaus Warnatz, MD a, b, Bodo Grimbacher, MD a, g, Jörg-Andres Rump, MD a, ‡, Michael Schlesier, PhD a, b, ‡Corresponding author: Jens Thiel, MD, Department of Rheumatology and Clinical Immunology, University Hospital Freiburg, Hugstetterstrasse 55, D-79106 Freiburg, Germany.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.
Le texte complet de cet article est disponible en PDF.Key words : CD21, complement receptor, hypogammaglobulinemia, common variable immunodeficiency, B lymphocyte
Abbreviations used : ⍺-kLC, BCR, CR, CVID, PnPS14
Plan
| Supported by the Deutsche Forschungsgemeinschaft (DFG)SFB 620 C1, SFB 620 C2 (U.S. and B.G.) and SFB 620 C7 (U.S.), by grant CCI-01E O0803 (K.W., H.E., and U.S.), by grants LSHM-CT-2004-005264 and EUROPADnet HEALTH-F2-2008-201549 of the European Union, and by a grant from the Hans Hench foundation. |
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| Disclosure of potential conflict of interest: K. Warnatz is a consultant for Medisys Health and has received research support from the Federal Ministry for Education and Research (BMBF). The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 3
P. 801 - mars 2012 Retour au numéro
Article précédent
- Pneumococcal polysaccharide vaccine at 12 months of age produces functional immune responses
- Paul V. Licciardi, Anne Balloch, Fiona M. Russell, Robert L. Burton, Jisheng Lin, Moon H. Nahm, Edward K. Mulholland, Mimi L.K. Tang
- CD21 deficiency, complement, and the development of common variable immunodeficiency
- Michael M. Frank
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