Functional B7.2 and B7-H2 Molecules on Myeloma Cells Are Associated with a Growth Advantage
Functional B7.2 and B7-H2 Molecules on Myeloma Cells Are Associated with a Growth Advantage
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DOI：
10.1158/1078-0432.ccr-08-0501
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发表时间：
2009-02-01
影响因子：
11.5
通讯作者：
Ogata, Kiyoyuki
中科院分区：
文献类型：
--
作者：
Yamashita, Thishi;Tamura, Hideto;Ogata, Kiyoyuki
目的：B7家族分子在抗原呈递细胞上表达，刺激或抑制正常的免疫应答。本研究的目的是调查是否功能B7.2和B7-H2分子表达的骨髓瘤细胞，如果是这样，他们是否与病理生理学在myeloma.Experimental Design：正常血浆和肿瘤（骨髓瘤）浆细胞的B7.2和B7-H2分子的表达进行了分析。结果：人骨髓瘤细胞系普遍表达B7.2和B7-H2分子，B7.2和B7-H2分子的表达与骨髓瘤细胞的增殖和免疫调节功能有关。浆细胞B7.2表达在骨髓瘤患者（n = 35）中比在意义不明的单克隆丙种球蛋白病患者（n = 12）或血液学正常个体（n = 10）中更常见。仅在骨髓瘤患者中观察到表达B7-H2的浆细胞，尽管很少。骨髓瘤细胞显示B7.2高表达的患者比其他骨髓瘤患者更容易贫血和贫血。通过用自体基质细胞或肿瘤坏死因子-a（骨髓瘤生物学中的关键细胞因子）培养骨髓瘤细胞来诱导或增强这些分子的表达。在所检查的人骨髓瘤细胞系中，与B7.2（-）和B7-H2（-）群体相比，B7.2（+）和B7-H2（+）群体中的细胞增殖更快。结论：骨髓瘤细胞表面的B7.2和B7-H2分子可能参与骨髓瘤的病理生理过程。
Purpose: B7 family molecules expressed on antigen-presenting cells stimulate or inhibit normal immune responses. The aim of this study was to investigate whether functional B7.2 and B7-H2 molecules are expressed on myeloma cells and, if so, whether they are associated with pathophysiology in myeloma.Experimental Design: The expression of B7.2 and B7-H2 molecules on normal plasma and neoplastic (myeloma) plasma cells was analyzed. The cell proliferation and immunomodulatory function of myeloma cells related to B7.2 and B7-H2 expression were examined.Results: Human myeloma cell lines commonly expressed B7.2 and B7-H2 molecules. B7.2 expression on plasma cells was more common in myeloma patients (n = 35) compared with that in patients with monoclonal gammopathy of unknown significance (n = 12) or hematologically normal individuals (n = 10). Plasma cells expressing B7-H2 were observed in myeloma patients alone, although rarely. Patients whose myeloma cells showed high B7.2 expression were more anemic and thrombocytopenic than other myeloma patients. The expression of these molecules was induced or augmented by cultivating myeloma cells with autologous stroma cells or tumor necrosis factor-a, a key cytokine in myeloma biology. Cell proliferation was more rapid in the B7.2(+) and B7-H2(+) populations compared with the B7.2(-) and B7-H2(-) populations, respectively, in the human myeloma cell lines examined. B7.2 and B7-H2 molecules on myeloma cells induced normal CD4(+) T cells to proliferate and produce soluble factors, including interleukin-10 that stimulate myeloma cell proliferation.Conclusions: Functional B7.2 and B7-H2 molecules detected on myeloma cells may be involved in the pathophysiology of myeloma.