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慢性淋巴细胞白血病中异源杂交体及其亲代B细胞细胞因子的表达与产生

Expression and production of cytokines by heterohybrids and their parental B cells in CLL.

作者信息

Diaw L, Lefebvre d'Hellencourt C, Cornillet I, Vuillier F, Guenounou M, Dighiero G

机构信息

Unite d'Immunohematologie, Institut Pasteur, Paris, France.

出版信息

Leuk Lymphoma. 1996 Apr;21(3-4):281-91. doi: 10.3109/10428199209067609.

DOI:10.3109/10428199209067609
PMID:8726409
Abstract

Three hybrids derived from CD5+ B cell chronic lymphocytic leukemia (B-CLL) and their parental B cells were studied for phenotypic evolution, immunoglobulin (Ig), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) secretion. When phenotypic evolution was examined, hybrids showed the loss of classical B cell markers, indicating that they follow the same pattern of phenotypic differentiation as normal B cells. Hybrids displayed spontaneous high Ig secretion, which did not appear to be modified through stimulation by phorbol 12-myristate 13-acetate (PMA), recombinant interferon-gamma (rIFN-gamma) and Staphylococcus aureus Cowan I (SAC). Parental cells secreted minimal amounts of Ig spontaneously or through IFN-gamma and SAC stimulation, whereas PMA succeeded in increasing this secretion. An opposite pattern was observed when TNF-alpha and IL-6 secretion an expression at the mRNA level were assessed in hybrids and parental cells. TNF-alpha and IL-6 were spontaneously secreted by parental cells and this secretion was increased after PMA and SAC stimulation, both cytokine secretion and expression at the mRNA level were negative in hybrid cells. The absence of expression of these cytokines could be explained either by chromosomal loss or by down regulation. These results indicate that when parental CLL cells are induced to differentiate in the heterohybrid model, they acquire high spontaneous secretion of Ig, lose the classical B cell phenotypic markers and down regulate the expression of the cytokines studied.

摘要

对源自CD5 + B细胞慢性淋巴细胞白血病(B - CLL)的三个杂交细胞及其亲代B细胞进行了表型演变、免疫球蛋白(Ig)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)分泌的研究。在检查表型演变时,杂交细胞显示出经典B细胞标志物的丧失,这表明它们遵循与正常B细胞相同的表型分化模式。杂交细胞表现出自发性高Ig分泌,这种分泌似乎不会因佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯(PMA)、重组干扰素-γ(rIFN-γ)和金黄色葡萄球菌Cowan I(SAC)的刺激而改变。亲代细胞自发分泌极少量的Ig,或通过IFN-γ和SAC刺激分泌,而PMA成功增加了这种分泌。当在杂交细胞和亲代细胞中评估TNF-α和IL-6分泌以及mRNA水平的表达时,观察到相反的模式。TNF-α和IL-6由亲代细胞自发分泌,PMA和SAC刺激后这种分泌增加,杂交细胞中的细胞因子分泌和mRNA水平的表达均为阴性。这些细胞因子表达的缺失可以通过染色体丢失或下调来解释。这些结果表明,当亲代CLL细胞在异源杂交模型中被诱导分化时,它们获得了高自发性Ig分泌,失去了经典B细胞表型标志物,并下调了所研究细胞因子的表达。

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