Burkitt's lymphomas express VH genes with a moderate number of antigen-selected somatic mutations.
Burkitt's lymphomas express VH genes with a moderate number of antigen-selected somatic mutations.
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伯基特淋巴瘤表达具有中等数量的抗原选择体细胞突变的 VH 基因。
作者：
J. Tamaru;M. Hummel;T. Marafioti;B. Kalvelage;L. Leoncini;C. Minacci;P. Tosi;D. Wright;H. Stein
伯基特淋巴瘤（BL）中肿瘤性B细胞的正常对应物是一个有争议的争论问题。为了澄清这一问题，半巢式引物聚合酶链反应进行扩增VDJ重排的免疫球蛋白重链（VH）基因的DNA提取物从10例（8散发和2地方性）BL病例。对所得扩增物进行测序以与已知的种系VH区段进行比较。对照病例包括6例B细胞慢性淋巴细胞白血病和6例套细胞淋巴瘤，已知显示幼稚非突变，即，前生发中心VH构型;和8例滤泡中心淋巴瘤，已知显示突变的VH基因，具有仍在进行的突变反应的迹象，这是生发中心细胞和由此衍生的淋巴瘤的特征。这种方法的结果显示，散发性和地方性BL表达突变的VH基因，突变频率（分别为4.9%和5.4%）明显低于滤泡中心淋巴瘤（11.8%）。此外，亚克隆扩增物后，序列分析显示没有正在进行的突变的迹象。这些结果使我们得出结论：BL中的肿瘤性B细胞的来源肯定不是来自幼稚的、未突变的前生发中心B细胞。相反，我们的研究结果支持BL细胞来源于在最初的超突变反应后被抑制的早期中心母细胞，或来源于生发中心B细胞，这些细胞在表面免疫球蛋白谱和突变模式方面已经分化，但在形态学和增殖方面没有向SIgM+ IgD-记忆B细胞分化，因为c-myc基因表达失调。
The normal counterpart of the neoplastic B cells occurring in Burkitt's lymphomas (BL) is an issue of controversial debate. To clarify this matter, a semi-nested primer polymerase chain reaction was performed to amplify the VDJ rearrangements of the immunoglobulin heavy chain (VH) gene of DNA extracts from 10 (8 sporadic and 2 endemic) BL cases. The resulting amplificates were sequenced for comparison with known germ line VH segments. The control cases comprised six cases of B cell chronic lymphocytic leukemia and six cases of mantle cell lymphoma known to display naive nonmutated, ie, pre-germinal center VH configurations; and eight cases of follicular center lymphoma known to display mutated VH genes with signs of a still-ongoing mutation reaction, characteristic for germinal center cells and lymphomas that derive therefrom. The results of this approach revealed that both sporadic and endemic BL express mutated VH genes with a mutation frequency considerably lower (4.9% and 5.4%, respectively) than that observed in follicular center lymphoma (11.8%). In addition, after subcloning the amplificates, sequence analysis revealed no signs of ongoing mutations. These results led us to conclude that the derivation of neoplastic B cells in BL is definitely not from naive, nonmutated pre-germinal center B cells. Instead, our findings support the view that BL cells stem either from early centroblasts that are arrested after an initial hypermutation reaction, or from germinal center B cells that have differentiated in terms of surface immunoglobulin profile and mutation pattern but not in terms of morphology and proliferation toward SIgM+ IgD- memory B cells because of the deregulated c-myc gene expression.