Vilpo Juhani, Tobin Gerard, Hulkkonen Janne, Hurme Mikko, Thunberg Ulf, Sundström Christer, Vilpo Leena, Rosenquist Richard
Department of Clinical Chemistry, University of Tampere Medical School and Laboratory Center of Tampere University Hospital, Tampere, Finland.
Eur J Haematol. 2005 Jul;75(1):34-40. doi: 10.1111/j.1600-0609.2005.00443.x.
To determine whether the immunoglobulin V(H) gene mutational status has an effect on the activation, proliferation and surface antigen expression of chronic lymphocytic leukemia (CLL) cells when stimulated in vitro.
The proliferation and activation responses of CLL cells were studied in 22-immunoglobulin gene V(H) unmutated (UM-CLL) and 12 hypermutated (M-CLL) CLL cases in 4-day cultures. As the mitogen responses have been previously shown to be diverse in CLL, a case-specific strategy based on optimized mitogen combinations (OMCs) of interleukin-2 (IL-2), 12-O-tetradecanoylphorbol 13-acetate (TPA), Staphylococcus aureus Cowan 1 (SAC), and human recombinant tumor necrosis factor alpha (TNF) was applied in cell stimulation. The expression of 23 surface membrane antigens (CD5, CD11c, CD19, CD20, CD21, CD22, CD23, CD25, CD27, CD38, CD40, CD45, CD45RA, CD45RO, CD79b, CD80, CD95, CD124, CD126, CD130, FMC7, IgD, and IgM) was studied by flow cytometry at days 0 and 4.
The proliferation and activation responses were similar in UM-CLL and M-CLL when OMCs contained IL-2, TPA or TNF. SAC induced faster proliferation in UM-CLL than in M-CLL. OMC stimulation induced preferential down-regulation of growth- promoting cell surface receptors CD5, CD21, and CD124 and preferential up-regulation of growth-inhibiting antigen CD80 in M-CLL.
Difference in immunophenotypic evolution of UM-CLL and M-CLL can be demonstrated if appropriate matrix signals are provided. The pathways for CD5, CD21, CD124 (IL4R), and CD80 (B7-1) regulation should be further explored in relation with somatic hypermutation and outcome of CLL.
确定免疫球蛋白V(H)基因突变状态在体外刺激时是否对慢性淋巴细胞白血病（CLL）细胞的激活、增殖及表面抗原表达产生影响。
在4天的培养中，对22例免疫球蛋白基因V(H)未突变（UM-CLL）和12例高突变（M-CLL）的CLL病例的CLL细胞的增殖和激活反应进行研究。由于先前已证明CLL中的促有丝分裂原反应具有多样性，因此在细胞刺激中采用了基于白细胞介素-2（IL-2）、12-O-十四烷酰佛波醇-13-乙酸酯（TPA）、金黄色葡萄球菌Cowan 1（SAC）和人重组肿瘤坏死因子α（TNF）的优化促有丝分裂原组合（OMC）的病例特异性策略。在第0天和第4天通过流式细胞术研究23种表面膜抗原（CD5、CD11c、CD19、CD20、CD21、CD22、CD23、CD25、CD27、CD38、CD40、CD45、CD45RA、CD45RO、CD79b、CD80、CD95、CD124、CD126、CD130、FMC7、IgD和IgM）的表达。
当OMC包含IL-2、TPA或TNF时，UM-CLL和M-CLL中的增殖和激活反应相似。SAC诱导UM-CLL中的增殖比M-CLL更快。OMC刺激诱导M-CLL中促生长细胞表面受体CD5、CD21和CD124的优先下调以及生长抑制抗原CD80的优先上调。
如果提供适当的基质信号，可证明UM-CLL和M-CLL在免疫表型演变上的差异。应进一步探讨CD5、CD21、CD124（IL4R）和CD80（B7-1）调节途径与CLL体细胞超突变和转归的关系。
