Rassenti L Z, Kipps T J
Department of Medicine, University of California, San Diego, La Jolla 92093-0663.
J Exp Med. 1993 Apr 1;177(4):1039-46. doi: 10.1084/jem.177.4.1039.
B cell chronic lymphocytic leukemia (CLL) is a malignancy of the CD5+ B cells. Prior studies indicated that CLL B cells generally express immunoglobulin (Ig) VH and VL genes with little or no somatic mutations. However, a recent report indicated that VH251, one of three VH genes belonging to the VH5 subgroup (e.g., VH251, VH32, and VH15), not only is frequently rearranged in this disease, but also has extensive and selective mutations when expressed by CLL B cells. The extent and nature of these mutations contrasts markedly from the low level of mutations noted in VH5 genes used by normal B cells or other Ig V genes found expressed in CLL. To determine whether this difference reflects a unique property of VH251 or a previously unrecognized subgroup of CLL, we examined for VH5 Ig gene rearrangements in leukemia cells from 68 patients that satisfied clinical and diagnostic criteria for CD5+ B cell CLL. Southern blot hybridization studies with probes for VH251 and the JH locus revealed that only 7 (10%) of the 68 monoclonal CLL cell populations had undergone Ig gene rearrangement involving VH5 genes. Two (3%) were found to have functionally rearranged VH5 genes that shared > or = 98% sequence homology with 5-2R1, a VH251 gene isolated from a pre-B cell acute lymphocytic leukemia. The other five CLL (7%) had functionally rearranged VH5 genes that each shared > or = 99% nucleic acid sequence homology with a germline VH32 isolated from human sperm DNA. These data indicate that VH251 or VH32 also may be expressed by CD5+ CLL B cells with little or no somatic mutation. These findings contrast with a recently published study on VH5 gene expression in B CLL and contest the hypothesis that extensive somatic mutation is a common property of the VH5 genes used in this disease. Further work to define the clinical and/or phenotypic characteristics of patients with leukemia cells that express mutated versus nonmutated Ig V genes may reveal subsets of CLL that possibly differ in their cytogenesis, etiopathogenesis, and/or clinical behavior.
B细胞慢性淋巴细胞白血病（CLL）是CD5+B细胞的恶性肿瘤。先前的研究表明，CLL B细胞通常表达免疫球蛋白（Ig）VH和VL基因，体细胞突变很少或没有。然而，最近的一份报告指出，VH251是属于VH5亚组的三个VH基因之一（例如，VH251、VH32和VH15），不仅在这种疾病中经常重排，而且当由CLL B细胞表达时具有广泛的选择性突变。这些突变的程度和性质与正常B细胞使用的VH5基因或CLL中发现表达的其他Ig V基因中观察到的低水平突变明显不同。为了确定这种差异是反映了VH251的独特特性还是CLL的一个先前未被认识的亚组，我们检查了68例符合CD5+B细胞CLL临床和诊断标准的患者白血病细胞中的VH5 Ig基因重排。用VH251和JH基因座探针进行的Southern印迹杂交研究表明，68个单克隆CLL细胞群体中只有7个（10%）发生了涉及VH5基因的Ig基因重排。发现两个（3%）具有功能重排的VH5基因，与从B前体淋巴细胞急性淋巴细胞白血病中分离的VH251基因5-2R1具有≥98%的序列同源性。另外五个CLL（7%）具有功能重排的VH5基因，每个基因与从人精子DNA中分离的种系VH32具有≥99%的核酸序列同源性。这些数据表明，VH251或VH32也可能由几乎没有或没有体细胞突变的CD5+CLL B细胞表达。这些发现与最近发表的一项关于B CLL中VH5基因表达的研究形成对比，并对广泛的体细胞突变是该疾病中使用的VH5基因的共同特性这一假设提出质疑。进一步确定表达突变与未突变Ig V基因的白血病细胞患者的临床和/或表型特征的工作可能会揭示CLL的亚组，这些亚组在细胞发生、病因发病机制和/或临床行为上可能有所不同。
