Dardick I, Sinnott N M, Hall R, Bajenko-Carr T A, Setterfield G
Am J Pathol. 1983 Apr;111(1):35-49.
One of the major tenets of current non-Hodgkin's lymphoma classifications is the relationship of morphologic subtypes to stages in the sequence of normal B-lymphocyte transformation occurring in the germinal follicle. To test this hypothesis, quantitative morphometric image analysis was carried out on in vivo and in vitro samples of mouse splenic lymphocytes in which transformation was induced by bacterial lipopolysaccharide (LPS), a specific B-cell mitogen. The results were compared with a similar analysis of germinal center lymphocyte populations of normal human spleen. In the in vivo mouse model, initial stages of B-cell transformation were detectable as early as 4 hours after LPS injection, and the process was essentially fully developed by 48-72 hours. Quantitative evaluation revealed that the majority of nuclear profiles were nearly spherical or only slightly eccentric and that no major alteration in nuclear contour occurred during any phase of the progressive increase in nuclear size following mitogen-induced lymphocyte transformation. In fact, in this system, B lymphocytes with a nuclear profile cleft of greater than or equal to 0.4 mu accounted for only 3% of the combined unstimulated and LPS-activated population assessed (N = 9936). This compared with normal human spleen, in which 16% of germinal center lymphocyte populations had similarly cleft nuclear profiles. Sequential alterations in the organization of condensed chromatin occurred concomitant with gradual nuclear enlargement during mitogen-induced mouse spleen lymphocyte transformation. A comparative morphologic and morphometric assessment of nuclear profiles of lymphocyte populations in germinal centers of normal human spleen provides indirect evidence for a similar pattern of nuclear alterations in human B lymphocytes. Autoradiographic data obtained from LPS-activated mouse splenic lymphocytes indicate that nuclear morphologic aspects of the transformation process can occur entirely within the G1 phase of the cell cycle. The results of this study suggest that subtypes of non-Hodgkin's lymphoma largely composed of neoplastic lymphocytes with extensively convoluted or cleft nuclei do not reflect a morphologic stage in the transformation of normal lymphocytes. In addition, the heterogeneous nuclear forms of follicular center cell lymphocytes would appear to result from parallel transformation processes involving cleaved and noncleaved nucleated lymphocytes and not the sequential pathway proposed by Lukes and Collins.
当前非霍奇金淋巴瘤分类的主要原则之一是形态学亚型与生发滤泡中正常B淋巴细胞转化序列各阶段的关系。为验证这一假说，对小鼠脾淋巴细胞的体内和体外样本进行了定量形态计量图像分析，这些样本中的转化由细菌脂多糖（LPS）诱导，LPS是一种特异性B细胞有丝分裂原。将结果与对正常人脾生发中心淋巴细胞群体的类似分析进行比较。在体内小鼠模型中，B细胞转化的初始阶段最早在LPS注射后4小时即可检测到，该过程在48 - 72小时基本完全发育。定量评估显示，大多数核轮廓近乎球形或仅略有偏心，并且在有丝分裂原诱导的淋巴细胞转化后核大小逐渐增加的任何阶段，核轮廓均未发生重大改变。事实上，在这个系统中，核轮廓裂隙大于或等于0.4微米的B淋巴细胞仅占评估的未刺激和LPS激活群体总和的3%（N = 9936）。相比之下，正常人脾中16%的生发中心淋巴细胞群体有类似裂隙的核轮廓。在有丝分裂原诱导的小鼠脾淋巴细胞转化过程中，浓缩染色质组织的顺序改变与核的逐渐增大同时发生。对正常人脾生发中心淋巴细胞群体核轮廓的比较形态学和形态计量评估为人类B淋巴细胞中类似的核改变模式提供了间接证据。从LPS激活的小鼠脾淋巴细胞获得的放射自显影数据表明，转化过程的核形态学方面可完全发生在细胞周期的G1期。本研究结果表明，主要由具有广泛卷曲或裂隙核的肿瘤性淋巴细胞组成的非霍奇金淋巴瘤亚型并不反映正常淋巴细胞转化的形态学阶段。此外，滤泡中心细胞淋巴细胞的异质核形态似乎是由涉及裂解和未裂解有核淋巴细胞的平行转化过程导致的，而非Lukes和Collins提出的顺序途径。
