Department of Rheumatology and Clinical Immunology, University Hospital Freiburg, Freiburg, Germany.
J Allergy Clin Immunol. 2012 Mar;129(3):801-810.e6. doi: 10.1016/j.jaci.2011.09.027. Epub 2011 Oct 27.
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.
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.
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.
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.
Genetic CD21 deficiency adds to the molecular defects observed in human subjects with hypogammaglobulinemia.
补体受体 2（CR2/CD21）是 B 细胞辅助受体的一部分，由成熟 B 细胞和滤泡树突状细胞表达。CD21 是 C3d 调理免疫复合物的受体，增强抗原特异性 B 细胞反应。
小鼠 CR2 基因座的基因失活导致体液免疫反应受损。在这里，我们报告了人类首例 CD21 遗传缺陷病例。
通过流式细胞术和 Western blot 分析 CD21 蛋白表达。通过实时 PCR 定量 CD21 转录物。对 CD21 基因进行测序。在转染 293T 细胞后，研究野生型和突变型 CD21 cDNA 的表达。通过流式细胞术分析 EBV-gp350 或含 C3d 的免疫复合物与 CD21 缺陷 B 细胞的结合以及钙流的诱导。测量对蛋白质和多糖疫苗的抗体反应。
一名 28 岁男性出现反复感染、类别转换记忆 B 细胞减少和低丙种球蛋白血症。CD21 受体表达不可检测。C3d 结合免疫复合物和 EBV-gp350 与 B 细胞的结合严重减少。序列分析显示 CD21 基因存在复合杂合的有害突变。用抗免疫球蛋白和 C3d 结合免疫复合物进行的功能研究表明，C3d 在增强亚最佳 B 细胞受体刺激中的共刺激活性完全丧失。对蛋白质抗原的疫苗接种反应正常，但对肺炎球菌多糖疫苗的接种反应中度受损。
CD21 遗传缺陷增加了人类低丙种球蛋白血症患者观察到的分子缺陷。
