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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Distinct Dynamics of Mitotic Transition in B-Cell Lymphoma and Reactive B-Cell Lymphoproliferations Determined by H3S10 Phosphohistone Immunolabeling
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Distinct Dynamics of Mitotic Transition in B-Cell Lymphoma and Reactive B-Cell Lymphoproliferations Determined by H3S10 Phosphohistone Immunolabeling

机译：H3S10磷酸酐免疫标记测定的B细胞淋巴瘤和反应性B细胞淋巴淋巴淋巴糊化物的不同动力学

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Objectives: Clonal selection in the follicular germinal centers in lymphatic tissues is accompanied by an intense proliferation of polyclonal B cells in a precisely regulated fashion. In contrast, B-cell neoplasias proliferate autonomously due to endogenous stimuli. The cell kinetic activity is obvious at many levels including progressive chromatin modification and elevated mitotic rates. We asked if there are differences in the kinetics of histone H3S10 phosphorylation required for mitotic entry between highly proliferating B cells of reactive germinal centers and in B-cell lymphomas with different proliferative capacity. Material and Methods: Phospho-H3 histone (pH3S10)-specific immunohistochemistry was applied to cultivated cell, reactive and selected indolent and aggressive lymphoma samples (diffuse large B-cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, follicular lymphoma and small lymphocytic lymphoma). Microscopic quantification of the "dot-type" (representing late G(2) phase) and "mitotic" immunolabeling patterns per field of view was performed and compared with classical cell proliferation markers. Results: In addition to the dense homogeneous chromatin labeling highlighting mitotic figures, we stated a selective dot-type nuclear labeling representing ongoing chromatin condensation in premitotic G(2) phase cells. While cell proliferation and mitotic counts correlated in general with histology, statistical analysis indicated an accumulation of G(2) phase pH3S10 pattern in the reactive germinal centers in contrast to lymphomas. The dot-type G(2) staining pattern was surprisingly overrepresented (1,321.7 +/- 356.5/10 HPF) in the reactive germinal centers compared to aggressive lymphomas (101.3 +/- 33.1) (p 0.005). The relative G(2)/M value was significantly higher (4.6 +/- 0.6) in reactive germinal center B cells than in any lymphoma entity evaluated (0.7 +/- 0.2 in Burkitt lymphoma, 0.9 +/- 0.4 in grade 3b follicular lymphoma, 1.3 +/- 1.1 in diffuse large B-cell lymphoma, 1.5 +/- 0.6 in lymphoblastic lymphoma, and 0.9 +/- 0.2 in small lymphocytic lymphoma). Conclusions: pH3S10 immunohistochemistry enabled the presentation of significant differences in the cell cycle kinetics between reactive and neoplastic B-cell lymphoproliferations. Accumulation of G(2) phase B cells in reactive folliculi directs to physiological G(2)/M checkpoint blockade. In contrast, accelerated G(2)/M transition in lymphomas is potentially associated with impaired genomic repair and cell death mechanisms. (C) 2017 S. Karger AG, Basel
机译：目的：淋巴组织中滤泡生发中心的克隆选择伴随着精确调节的时装中多克隆B细胞的强烈增殖。相反，由于内源性刺激，B细胞肿瘤瘤增殖自主。细胞动力学活性在许多水平下显而易见，包括渐进式染色质修饰和升高的有丝分裂率。我们询问是否存在组蛋白H3S10的动力学存在差异，在具有不同增殖能力的高增殖B细胞和具有不同增殖能力的B细胞淋巴瘤之间进行有丝分裂性磷酸化的磷酸化。材料和方法：将磷酸-H3组蛋白（PH3S10） - 特异性免疫组织化应用于培养的细胞，反应性和选定的惰性和腐蚀性淋巴瘤样品（弥漫性大B细胞淋巴瘤，Burkitt淋巴瘤，淋巴细胞淋巴瘤，滤色淋巴瘤和小淋巴细胞淋巴瘤）。对每个视野进行“点型”（代表G（2）相）和“有丝分​​裂”免疫标记图案的微观定量化并与经典细胞增殖标志物进行比较。结果：除了致密均匀的染色质标记突出显示有丝分裂图外，我们还表明了一种选择性点型核标记，代表了在原种子的G（2）相细胞中的持续染色质凝结。虽然细胞增殖和有丝分裂计数与组织学相一般相关，但统计学分析表明与淋巴瘤相比，反应性生发中心中的G（2）相pH3S10模式的积累。与腐蚀性淋巴瘤（101.3 +/- 33.1）（P <0.005）相比，DOT型G（2）染色模式令人惊讶的是反应生发中心中的过度呈现（1,321.7 +/- 356.5 / 10 HPF）（P <0.005）。反应性生发中心B细胞中的相对g（2）/ m值明显高于（4.6 +/- 0.6），而不是在评估的任何淋巴瘤实体中（3.7 +/- 0.2，在3B级滤泡级为0.9 +/- 0.4淋巴瘤，1.3 +/- 1.1在弥漫性大B细胞淋巴瘤中，淋巴细胞淋巴瘤的1.5 +/- 0.6，小淋巴细胞淋巴瘤的0.9 +/- 0.2）。结论：PH3S10免疫组织化学使能活性和肿瘤B细胞淋巴抑制晶体间细胞周期动力学呈现显着差异。反应性Folliculi中G（2）相B细胞的累积指示生理g（2）/ m检查点封闭。相反，淋巴瘤中的加速G（2）/ m转变可能与基因组修复和细胞死亡机制受损。 （c）2017年S. Karger AG，巴塞尔

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