VH1-69 gene is preferentially used by hepatitis C virus-associated B cell lymphomas and by normal B cells responding to the E2 viral antigen
VH1-69 gene is preferentially used by hepatitis C virus-associated B cell lymphomas and by normal B cells responding to the E2 viral antigen
复制标题
DOI：
10.1182/blood.v97.4.1023
复制
发表时间：
2001-02-15
期刊：
影响因子：
20.3
通讯作者：
Levy, S
中科院分区：
文献类型：
--
作者：
Chan, CH;Hadlock, KG;Levy, S
丙型肝炎病毒 (HCV) 相关 B 细胞淋巴瘤先前被证明表达有限的免疫球蛋白 V-H 和 V-L 基因库，分别为 V(H)1-69 和 V(K)A27。尽管这表明抗原选择在这些淋巴瘤的发病机制中发挥作用，但参与克隆扩增的驱动抗原尚未确定。在无症状 HCV 感染患者中分析了 B 细胞对病毒抗原 HCV 包膜糖蛋白 2 (E2) 的反应。永生化为杂交瘤并选择结合 E2 的单个 B 细胞，分析其 V 基因的使用情况。这些V区基因的序列表明每个杂交瘤表达独特的V-H和V-L基因。值得注意的是，这些抗 E2 杂交瘤优先使用 V(H)1-69 基因。替换突变与沉默突变比率的分析表明，这些基因经历了体细胞突变和抗原选择。在另一份报告中，人类抗 E2 抗体也显示出表达相同的 V-H 基因。这些数据强化了 HCV 相关淋巴瘤源自 HCV 刺激的克隆扩增 B 细胞的假设。 (C) 2001 年，美国血液学会。
Hepatitis C virus (HCV)-associated B cell lymphomas were previously shown to express a restricted repertoire of immunoglobulin V-H and V-L genes, V(H)1-69 and V(K)A27, respectively. Although this suggests a role for antigen selection in the pathogenesis of these lymphomas, the driving antigen involved in the clonal expansion has not been identified. B cell response to a viral antigen, the HCV envelope glycoprotein 2 (E2), was analyzed in an asymptomatic HCV-infected patient. Single B cells, immortalized as hybridomas and selected for binding E2, were analyzed for their V gene usage. Sequences of these V region genes demonstrated that each hybridoma expressed unique V-H and V-L genes. Remarkably, these anti-E2 hybridomas preferentially used the V(H)1-69 gene. Analysis of replacement to silent mutation ratios indicated that the genes underwent somatic mutation and antigenic selection. In a separate report, human anti-E2 antibodies were also shown to express the same V-H gene. These data strengthen the hypothesis that the HCV-associated lymphomas are derived from clonally expanded B cells stimulated by HCV. (C) 2001 by The American Society of Hematology.