Role of BAFF in Opsoclonus‐Myoclonus syndrome, a bridge between cancer and autoimmunity
Role of BAFF in Opsoclonus‐Myoclonus syndrome, a bridge between cancer and autoimmunity
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DOI：
10.1189/jlb.0213106
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发表时间：
2013-07
影响因子：
5.5
通讯作者：
L. Raffaghello;Verena Fuhlhuber;G. Bianchi;M. Conte;F. Blaes;C. Gambini;V. Pistoia
中科院分区：
文献类型：
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作者：
L. Raffaghello;Verena Fuhlhuber;G. Bianchi;M. Conte;F. Blaes;C. Gambini;V. Pistoia
OMS是一种罕见的影响成人和儿童的副肿瘤疾病。小儿OMS常与NB相关，NB是一种常见的儿童期实体瘤，起源于交感神经系统。NB患者自身抗体和淋巴细胞浸润的检测提出了OMS相关NB发病机制的自身免疫假说。BAFF是一种有效的B细胞生长和存活调节剂，通过与受体BAFF - R和BCMA相互作用。本研究的目的是探讨OMS相关NB中异位淋巴样细胞新生的机制。我们研究了BAFF、BAFF - R和BCMA在与OMS相关或不相关的NB肿瘤中的表达。此外，我们评估了BAFF在分化剂处理或未处理的NB细胞系中的表达和分泌情况。免疫组化结果显示，不论有无OMS，浸润NB肿瘤的淋巴细胞均表达BAFF、BAFF‐R和BCMA，而成神经细胞表达BAFF和BCMA，但不表达BAFF‐R。流式细胞术发现BAFF在NB细胞系中一致表达。与组织病变的结果相似，在基础条件下，所有NB细胞系表面均检测到BCMA，但未检测到BAFF‐R。用IFN - γ或13 -顺式维甲酸处理NB细胞株，观察到BAFF - R的重新合成和BCMA的上调。这项研究为驱动淋巴滤泡新生的机制以及OMS相关NB中肿瘤和免疫细胞之间的功能相互作用提供了新的见解。
OMS is a rare paraneoplastic disorder that affects adults and children. Pediatric OMS is often associated with NB, a common, solid tumor of childhood, derived from the sympathetic nervous system. The detection of autoantibodies and lymphocytic infiltration in NB patients led to advance an autoimmune hypothesis for the pathogenesis of OMS‐related NB. BAFF is a potent modulator of B cell growth and survival upon interaction with its receptors BAFF‐R and BCMA. The aim of this study was to investigate mechanism(s) involved in ectopic lymphoid neogenesis in OMS‐associated NB. We investigated BAFF, BAFF‐R, and BCMA expression in NB tumors associated or not with OMS. Furthermore, we evaluated BAFF expression and secretion in NB cell lines, treated or untreated with differentiating agents. Immunohistochemically, lymphocytes infiltrating NB tumors from patients, with or without OMS, expressed BAFF, BAFF‐R, and BCMA, whereas neuroblasts expressed BAFF and BCMA but not BAFF‐R. By flow cytometry, BAFF was found to be consistently expressed in NB cell lines. Similarly to the results obtained in tissue lesions, BCMA but not BAFF‐R was detected on the surface of all NB cell lines under basal conditions. De novo synthesis of BAFF‐R and up‐regulation of BCMA were observed in NB cell lines upon treatment with IFN‐γ or 13‐cis retinoic acid. This study provides new insights in the mechanisms driving the neogenesis of lymphoid follicles and in the functional interactions between tumor and immune cells in OMS‐associated NB.