Taubenheim Nadine, von Hornung Marcus, Durandy Anne, Warnatz Klaus, Corcoran Lynn, Peter Hans-Hartmut, Eibel Hermann
Clinical Research Unit for Rheumatology, University Hospital of Freiburg, Freiburg, Germany.
J Immunol. 2005 Oct 15;175(8):5498-503. doi: 10.4049/jimmunol.175.8.5498.
Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by defective Ab production and recurrent bacterial infections. The largely unknown causes are likely to comprise a diverse set of genetic or acquired defects. In this study, we investigated terminal B cell differentiation in lymph nodes from CVID patients. Up to the germinal center B cell stage, B cell differentiation was normal but terminal plasma cell development was found to be impaired. Using differential Blimp-1 and Syndecan-1 expression in controls, we defined three different plasma cell subsets that correspond to progressive developmental stages locating to different sites in the lymph node. In the CVID patients, we could only detect one or two of these subsets indicating a defective differentiation. Thus, terminal plasma cell differentiation was found to be impaired despite normal expression of Blimp-1. B cells reaching only the first stage of plasma cell differentiation were further unable to undergo isotype switching and to up-regulate activation markers on B cells stimulated in vitro.
常见变异型免疫缺陷（CVID）是一种异质性疾病，其特征为抗体产生缺陷和反复发生细菌感染。其病因大多不明，可能包括多种遗传或后天获得性缺陷。在本研究中，我们调查了CVID患者淋巴结中B细胞的终末分化情况。直至生发中心B细胞阶段，B细胞分化均正常，但发现终末浆细胞发育受损。利用对照组中Blimp-1和Syndecan-1的差异表达，我们定义了三个不同的浆细胞亚群，它们对应于位于淋巴结不同部位的渐进性发育阶段。在CVID患者中，我们只能检测到其中一两个亚群，表明分化存在缺陷。因此，尽管Blimp-1表达正常，但终末浆细胞分化仍被发现受损。仅达到浆细胞分化第一阶段的B细胞进一步无法进行同种型转换，也无法上调体外刺激的B细胞上的活化标志物。
