Hummel M, Ziemann K, Lammert H, Pileri S, Sabattini E, Stein H
Institute of Pathology, Klinikum Benjamin Franklin, Freie Universität Berlin, Germany.
N Engl J Med. 1995 Oct 5;333(14):901-6. doi: 10.1056/NEJM199510053331403.
There is strong evidence that Reed-Sternberg cells have a lymphoid phenotype, but clonally rearranged genes for B-cell and T-cell antigen receptors have not been demonstrable in tumor tissue from most patients with Hodgkin's disease. To elucidate this issue, we assayed single Reed-Sternberg cells from 12 patients with classic Hodgkin's disease of a B-cell immunophenotype to detect rearranged immunoglobulin variable-region heavy-chain (VH) genes.
We isolated single Reed-Sternberg cells from frozen sections that had been immunostained for CD30. The rearranged VH genes of these cells were amplified by the polymerase chain reaction and analyzed by gel electrophoresis and nucleotide sequencing.
In all 12 patients, the Reed-Sternberg cells studied contained rearranged VH genes. Three patterns were observed: in three patients the rearrangements in each patient were identical, in six patients all the rearrangements were unrelated and unique, and in three patients both identical and unrelated rearrangements were detected. Apparently somatic mutations of VH genes were present in some Reed-Sternberg cells but absent in others.
Reed-Sternberg cells with B-cell phenotypes have rearranged VH genes; therefore, these cells arise from B cells. The pattern of VH gene mutations suggests that Reed-Sternberg cells can correspond to either immunologically naive or memory B cells. In half our patients the population of Reed-Sternberg cells was polyclonal; in the other half, monoclonal or mixed cell populations were found. Correlation with the clinical stage suggests that polyclonal Hodgkin's disease can present as a widespread lymphoma.
有强有力的证据表明里德-斯腾伯格细胞具有淋巴细胞表型，但在大多数霍奇金病患者的肿瘤组织中，尚未证实存在B细胞和T细胞抗原受体的克隆性重排基因。为阐明这一问题，我们检测了12例具有B细胞免疫表型的经典霍奇金病患者单个里德-斯腾伯格细胞中免疫球蛋白可变区重链（VH）基因的重排情况。
我们从经CD30免疫染色的冰冻切片中分离单个里德-斯腾伯格细胞。通过聚合酶链反应扩增这些细胞的重排VH基因，并进行凝胶电泳和核苷酸测序分析。
在所有12例患者中，所研究的里德-斯腾伯格细胞均含有重排的VH基因。观察到三种模式：3例患者中，每个患者的重排均相同；6例患者中，所有重排均不相关且独特；3例患者中，同时检测到相同和不相关的重排。部分里德-斯腾伯格细胞中存在VH基因的体细胞突变，而其他细胞中则不存在。
具有B细胞表型的里德-斯腾伯格细胞存在VH基因重排；因此，这些细胞起源于B细胞。VH基因突变模式表明，里德-斯腾伯格细胞可能对应免疫幼稚B细胞或记忆B细胞。在我们一半的患者中，里德-斯腾伯格细胞群体是多克隆的；在另一半患者中，发现了单克隆或混合细胞群体。与临床分期的相关性表明，多克隆性霍奇金病可表现为广泛的淋巴瘤。
