Baker B W, Deane M, Gilleece M H, Johnston D, Scarffe J H, Norton J D
CRC Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Leuk Lymphoma. 1994 Jul;14(3-4):291-301. doi: 10.3109/10428199409049681.
We have analysed the rearranged Ig heavy chain (IgH) genes in a series of 28 cases of multiple myeloma (MM), in order to extend the study of Ig heavy chain variable (VH) gene usage in B lymphoid malignancies and to explore the ontogenic compartment from which transformed precursor cells arise in this disease. We were able to amplify 28 rearranged alleles by polymerase chain reaction from 23 of these cases, using a common joining region (JH) amplimer together with a panel of VH family-specific amplimers. The pattern of VH family usage was similar to that reported in normal peripheral blood B cells with infrequent usage of VH5 and VH6 genes. However, nucleotide sequence analysis of 17 IgH alleles revealed rearrangement of other VH family members, closely related to known developmentally regulated VH genes, some of which are known to be associated with autoimmune specificities. In contrast to previous findings on more immature B lineage malignancies, the rearranged genes diverged extensively from consensus germline sequences, consistent with somatic mutation. These findings support the hypothesis that the major proliferating precursor in MM arises at, or following a stage of T cell-dependent germinal centre proliferation in lymphoid follicles.
我们分析了28例多发性骨髓瘤（MM）病例中重排的免疫球蛋白重链（IgH）基因，以扩展对B淋巴细胞恶性肿瘤中免疫球蛋白重链可变区（VH）基因使用情况的研究，并探索该疾病中转化前体细胞起源的个体发生区室。我们使用一个共同的连接区（JH）扩增引物和一组VH家族特异性扩增引物，通过聚合酶链反应从其中23例病例中扩增出28个重排等位基因。VH家族的使用模式与正常外周血B细胞中报道的相似，VH5和VH6基因的使用频率较低。然而，对17个IgH等位基因的核苷酸序列分析显示，其他VH家族成员发生了重排，这些成员与已知的发育调控VH基因密切相关，其中一些已知与自身免疫特异性相关。与之前关于更不成熟B系恶性肿瘤的研究结果相反，重排基因与种系共有序列有很大差异，这与体细胞突变一致。这些发现支持了这样一种假说，即MM中的主要增殖前体细胞产生于淋巴滤泡中T细胞依赖性生发中心增殖阶段或之后。
