Hsu F J, Levy R
Department of Medicine, Stanford University School of Medicine, CA, USA.
Blood. 1995 Oct 15;86(8):3072-82.
Ig heavy chain variable region (VH) genes expressed by human diffuse large-cell lymphoma (DLC) and follicular lymphoma (FL) were identified and analyzed with respect to germline gene families. In 67 cases of FL, VH region genes were expressed in a pattern similar to that of normal B cells, with a predominance of the large VH3 gene family being used. In contrast, of the 17 cases of DLC, there was an extremely biased use of VH genes. Of these DLC tumors, 88% expressed genes from the small VH4 gene family; and even among these tumors, there was a limited use of genes, with 11 cases producing Igs derived from the VH4.21 germline gene. Although most of the VH genes expressed by DLC tumor cells contained mutations with respect to their germline counterparts, almost all of these mutations occurred before the clonal expansion of the tumor. This contrasts with our previous findings of ongoing mutations in FL and represents a fundamental difference between these two malignancies. This preferential gene use implies an important role for the VH4 gene family, and specifically for VH4.21, in the genesis of DLC.
对人类弥漫性大细胞淋巴瘤（DLC）和滤泡性淋巴瘤（FL）所表达的免疫球蛋白重链可变区（VH）基因进行了鉴定，并就种系基因家族进行了分析。在67例FL中，VH区基因的表达模式与正常B细胞相似，主要使用的是较大的VH3基因家族。相比之下，在17例DLC中，VH基因的使用存在极大的偏向性。在这些DLC肿瘤中，88%表达的是来自较小VH4基因家族的基因；即便在这些肿瘤中，基因的使用也很有限，有11例产生的免疫球蛋白源自VH4.21种系基因。尽管DLC肿瘤细胞所表达的大多数VH基因与其种系对应基因相比含有突变，但几乎所有这些突变都发生在肿瘤的克隆扩增之前。这与我们之前在FL中发现的持续突变情况形成对比，代表了这两种恶性肿瘤之间的根本差异。这种对基因的优先使用意味着VH4基因家族，特别是VH4.21，在DLC的发生过程中发挥了重要作用。
