Circulating clonotypic B cells in classic Hodgkin lymphoma

Circulating clonotypic B cells in classic Hodgkin lymphoma
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DOI:
10.1182/blood-2008-11-189688
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发表时间:
2009-06-04
期刊:
影响因子:
20.3
通讯作者:
Matsui, William
Matsui, William
中科院分区:
医学1区
文献类型:
--
作者:
Jones, Richard J.;Gocke, Christopher D.;Matsui, William

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虽然霍奇金和里德-斯滕伯格(HRS)细胞是B淋巴细胞,但它们不同于该谱系的任何正常细胞。此外,HRS细胞有限的增殖潜力掩盖了霍奇金淋巴瘤(HL)的临床侵袭性。20多年前,据报道,L428 HL细胞系含有少量表型B细胞,这些细胞似乎负责HRS细胞的持续生成。然而,这一观察结果从未得到证实,并且从未在HL患者中记录过此类克隆型B细胞。我们发现,L428和KM-H2 HL细胞系都含有罕见的B细胞亚群,负责主要HRS细胞群的产生和维持。HL细胞系中的B细胞表达免疫球蛋白轻链、记忆B细胞抗原CD 27和干细胞标志物乙醛脱氢酶(ALDH)。在大多数新诊断的HL患者(无论分期)的血液中也检测到克隆性CD 27(+)ALDH(高)B细胞,与淋巴结HRS细胞共享免疫球蛋白基因重排。尽管循环克隆型B细胞在HL中的临床意义尚不清楚,但这些数据表明它们可能是HL的起始细胞。(血。2009; 113:5920-5926)
Although Hodgkin and Reed-Sternberg (HRS) cells are B lymphoid cells, they are unlike any normal cells of that lineage. Moreover, the limited proliferative potential of HRS cells belies the clinical aggressiveness of Hodgkin lymphoma (HL). More than 20 years ago, the L428 HL cell line was reported to contain a small population of phenotypic B cells that appeared responsible for the continued generation of HRS cells. This observation, however, has never been corroborated, and such clonotypic B cells have never been documented in HL patients. We found that both the L428 and KM-H2 HL cell lines contained rare B-cell subpopulations responsible for the generation and maintenance of the predominant HRS cell population. The B cells within the HL cell lines expressed immunoglobulin light chain, the memory B-cell antigen CD27, and the stem cell marker aldehyde dehydrogenase (ALDH). Clonal CD27(+)ALDH(high) B cells, sharing immunoglobulin gene rearrangements with lymph node HRS cells, were also detected in the blood of most newly diagnosed HL patients regardless of stage. Although the clinical significance of circulating clonotypic B cells in HL remains unclear, these data suggest they may be the initiating cells for HL. (Blood. 2009; 113: 5920-5926)