Haran-Ghera N, Peled A, Canaani E, Caspi Y, Haimovich J, Shaft D, Resnitzky P, Brightman B K, Fan H
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Leukemia. 1995 Nov;9(11):1940-7.
Prevention of high frequency spontaneous T cell lymphoma development in AKR mice by mAb 18-5 treatment was shown to involve inhibition of the recombinant Class I MCF virus formation and elimination of the early occurring potential lymphoma cells (PLCs). A low B cell lymphoma incidence (16% at a mean latency of 540 days) and a low level of PLCs (yielding 12% B cell lymphoma development following lymphoid cell transfer) was observed in mAb 18-5 treated mice (in contrast to a high PLC level in thymectomized AKR mice that could be experimentally triggered to progress to overt CD5+ B cell lymphomas). Administration of anti CD8 mAb or IL-4 to 12-month-old mAb 18-5 pre-treated mice only slightly increased B cell lymphoma incidence (up to 30-40%). Exposure to split-dose irradiation resulted in 26% B cell lymphomas at a 250 day mean latency. The phenotypes of the B lymphomas developing in mAb 18-5 treated mice were: B220+ (14.8+, 6B2+), 6C3+, Mac2+, CD5-. Most lymphomas expressed l-a and surface IgM, pointing to their mature B cell characteristics. Moreover, in some of the lymphomas, high levels of IgM production and secretion were determined. A comparison of the morphological characteristics (based on light and ultrastructure microscopy) of CD5+ and CD5- B cell lymphomas developing in AKR mice indicated marked differences. Analysis of the IgH locus of representative CD5- B lymphomas showed an identical pattern of IgH rearrangement in some tumors (similar to previous findings among CD5+ lymphomas). The virological analysis of the CD5- B cell lymphomas (similar to those observed in the CD5+ B cell lymphomas of AKR origin) showed that their development did not require formation of the pathogenic MCF recombinant viruses. The differences observed between the CD5+ and CD5- B cell lymphomas developing in AKR mice (following prevention of spontaneous T cell lymphomagenesis) may be due to their origin of different B cell precursors or from B cells at different levels of differentiation.
单克隆抗体18 - 5治疗可预防AKR小鼠发生高频自发性T细胞淋巴瘤，这一过程涉及抑制重组I类MCF病毒的形成以及清除早期出现的潜在淋巴瘤细胞（PLCs）。在接受单克隆抗体18 - 5治疗的小鼠中，观察到低水平的B细胞淋巴瘤发病率（平均潜伏期540天时为16%）和低水平的PLCs（淋巴细胞转移后产生12%的B细胞淋巴瘤）（与之形成对比的是，胸腺切除的AKR小鼠中PLC水平较高，可通过实验诱导发展为明显的CD5 + B细胞淋巴瘤）。给12月龄的经单克隆抗体18 - 5预处理的小鼠注射抗CD8单克隆抗体或白细胞介素 - 4，只会使B细胞淋巴瘤发病率略有增加（高达30 - 40%）。接受分次剂量照射后，平均潜伏期250天时B细胞淋巴瘤发病率为26%。在接受单克隆抗体18 - 5治疗的小鼠中发生的B淋巴瘤的表型为：B220 +（14.8 +，6B2 +）、6C3 +、Mac2 +、CD5 -。大多数淋巴瘤表达l - a和表面IgM，表明它们具有成熟B细胞的特征。此外，在一些淋巴瘤中，检测到高水平的IgM产生和分泌。对AKR小鼠中发生的CD5 +和CD5 - B细胞淋巴瘤的形态学特征（基于光学和超微结构显微镜观察）进行比较，发现存在显著差异。对代表性CD5 - B淋巴瘤的IgH基因座分析表明，一些肿瘤中IgH重排模式相同（类似于之前在CD5 +淋巴瘤中的发现）。对CD5 - B细胞淋巴瘤的病毒学分析（类似于在源自AKR的CD5 + B细胞淋巴瘤中观察到的情况）表明，它们的发展不需要致病性MCF重组病毒的形成。在AKR小鼠中（在预防自发性T细胞淋巴瘤发生后）观察到的CD5 +和CD5 - B细胞淋巴瘤之间的差异，可能是由于它们起源于不同的B细胞前体或处于不同分化水平的B细胞。
