Heterogeneous expression of interleukin-18 and its receptor in B-cell lymphoproliferative disorders deriving from naive, germinal center, and memory B lymphocytes
Heterogeneous expression of interleukin-18 and its receptor in B-cell lymphoproliferative disorders deriving from naive, germinal center, and memory B lymphocytes
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DOI：
10.1158/1078-0432.ccr-1026-3
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发表时间：
2004-01-01
影响因子：
11.5
通讯作者：
Pistoia, V
中科院分区：
文献类型：
--
作者：
Airoldi, I;Raffaghello, L;Pistoia, V
目的：细胞因子/细胞因子受体表达失调可能发生在B细胞淋巴增生性疾病中。关于正常和恶性B细胞中白细胞介素-18受体（IL-18 R）和IL-18表达的信息很少。我们的目的是调查这个问题，在人类幼稚，生发中心（GC）和记忆B细胞，并在他们的肿瘤people.Experimental Design：我们已经评估了IL-18的表达和生产扁桃体幼稚，GC和记忆B细胞，并在他们假定的肿瘤对应逆转录-PCR和ELISA。结果：（1）IL-18 mRNA在扁桃体幼稚细胞、GC细胞和记忆B细胞中均有表达，但在正常对照组和正常对照组中无表达。生物活性IL-18由初始和GC分泌，但不由记忆B细胞分泌;（B）IL-18 Ra和0转录物在三个B细胞亚群中表达。在幼稚、GC和记忆B淋巴细胞的表面上检测到IL-18 R α，并且在GC和记忆细胞上检测到IL-18 R β，但在幼稚、B细胞上未检测到IL-18 R β;（c）套区、滤泡、边缘区、伯基特淋巴瘤（BL）和B细胞慢性淋巴细胞白血病（B-CLL）细胞表达IL-18 mRNA。B-CLL和BL细胞不产生生物活性IL-18;和（d）淋巴瘤B细胞显示IL-18 R链mRNA之一或两者的异质性表达。相反，B-CLL细胞在mRNA和蛋白水平表达IL-18 R链。结论：慢性B细胞淋巴增生性疾病中IL-18和/或IL-18 R的表达失调有时可能导致肿瘤从宿主免疫系统逃逸。
Purpose: Dysregulated cytokine/cytokine receptor expression may occur in B-cell lymphoproliferative disorders. Little information is available on interleukin-18 receptor (IL-18R) and IL-18 expression in normal and malignant B cells. Our purpose was to investigate this issue in human naive, germinal center (GC) and memory B cells, and in their neoplastic counterparts.Experimental Design: We have evaluated IL-18 expression and production in tonsil naive, GC, and memory B cells and in their presumed neoplastic counterparts by reverse transcription-PCR and ELISA. Moreover, IL-18Ralpha and beta expression was investigated in the same cells by reverse transcription-PCR, flow cytometry, and immunohistochemistry.Results: We found that: (a) IL-18 mRNA was expressed in tonsil naive, GC, and memory B cells. Bioactive IL-18 was secreted by naive and GC, but not by memory B cells; (b) IL-18Ralpha and 0 transcripts were expressed in the three B-cell subsets. IL-18Ralpha was detected on the surface of naive, GC, and memory B lymphocytes, and IL-18Rbeta was detected on GC and memory, but not naive, B cells; (c) mantle zone, follicular, marginal zone, Burkitt lymphoma (BL), and B-cell chronic lymphocytic leukemia (B-CLL) cells expressed IL-18 mRNA. B-CLL and BL cells did not produce bioactive IL-18; and (d) lymphoma B-celis displayed heterogeneous expression of either or both IL-18R chain mRNA. In contrast, B-CLL cells expressed both IL-18R chains at the mRNA and protein levels. Conclusions: Dysregulated expression of IL-18 and/or IL-18R in chronic B-cell lymphoproliferative disorders may sometimes contribute to tumor escape from the host immune system.