FUNCTIONAL INTERACTION BETWEEN B-CELL SUBPOPULATIONS DEFINED BY CD23 EXPRESSION

FUNCTIONAL INTERACTION BETWEEN B-CELL SUBPOPULATIONS DEFINED BY CD23 EXPRESSION
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DOI:
10.1002/eji.1830181115
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发表时间:
1988-11-01
影响因子:
5.4
通讯作者:
GOFF, LK
GOFF, LK
中科院分区:
医学3区
文献类型:
--
作者:
ARMITAGE, RJ;GOFF, LK

文献摘要

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使用与磁珠结合的 CD23 单克隆抗体 (mAb) MHM6 和绵羊抗小鼠 Ig,我们获得了高度纯化的 MHM6+ 和 MHM6- toonsil B 细胞群。我们发现,激活后 B 细胞上 MHM6 反应性表达的增加是由于已经弱阳性的细胞上抗原的上调,而不是由于先前阴性细胞群上新抗原的表达。在存在抗 IgM (.alpha..mu.) 和白细胞介素 4 (IL4) 或 CDw40 mAb G28-5 以及金黄色葡萄球菌 Cowan I (SAC) 以及较小程度的佛波酯 12-O-十四烷酰佛波醇 13-乙酸酯 (TPA) 的情况下,观察到 MHM6+ 细胞的强烈增殖反应,与在未分级的 B 细胞。相反,单独培养的MHM6-群体仅对.alpha..mu反应较弱。 + G28-5 或 SAC,对 .alpha..mu 几乎没有反应。 + IL4 或 TPA。在所有这些促有丝分裂刺激下,通过添加丝裂霉素 C (MC) 处理的 MHM6+ 细胞,MHM6- 群体对氚化胸苷的摄取增加了三到六倍。用抗白细胞功能抗原 1 mAb 预处理细胞对 MHM6- 细胞群的后续增殖几乎没有影响,但表明细胞接触对于 MHM6+ 细胞的增殖至关重要。这种预处理揭示了 MHM6+ 和 MHM6- 细胞之间观察到的功能相互作用取决于细胞接触和 MHM6+ 细胞衍生的可溶性成分的存在。我们发现,添加从 Epstein-Barr 病毒转化的淋巴母细胞系上清液中纯化的可溶性 CD23,在灭活的 MHM6+ 细胞存在的情况下,会增加 MHM6-扁桃体 B 细胞对促有丝分裂刺激的增殖反应,但在 MHM6+ 细胞不存在时,对增殖没有影响。通过与正常 B 淋巴细胞对比,我们检查了幼淋巴细胞白血病 (PLL) B 细胞的功能反应。尽管这些细胞在新鲜分离时显示出与正常 B 细胞相当的 CD23 表达水平,但这种表达在激活后不会增加。此外,与正常 B 细胞相比,单独培养的 PLL MHM6- 群体对各种促有丝分裂刺激显示出强烈的增殖反应,与 mHM6+ 或未分级细胞的增殖反应相当,并且这种反应不会因添加 MC 处理的 MHM6+ 细胞而增强。因此,描述了正常 B 细胞群(而非白血病 B 细胞群)之间的一种新的功能相互作用,该 B 细胞群由其 CD23 的表达来定义。这种相互作用涉及两种成分,一种通过细胞接触介导,另一种通过源自 MHM6+ 细胞的可溶性因子的存在介导,两种成分单独均无效。
Using the CD23 monoclonal antibody (mAb) MHM6 and sheep anti-mouse Ig bound to magnetic beads we have obtained highly purified populations of MHM6+ and MHM6- toonsil B cells. We have found that the increased expression of MHM6 reactivity seen on B cells after activation results from up-regulation of antigen on cells already weakly positive and not from expression of new antigen on the previously negative population. The strong proliferative responses of MHM6+ cells seen in the presence of anti-IgM (.alpha..mu.) and interleukein 4 (IL4) or the CDw40 mAb G28-5, and with Staphylococcus aureus Cowan I (SAC), and to a lesser extent with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), resemble that seen among unfractionated B cells. In contrst, the MHM6- population cultured alone responds only weakly to .alpha..mu. + G28-5 or SAC and exhibits virtually no response to .alpha..mu. + IL4 or TPA. With all these mitogenic stimuli, tritiated thymidine uptake by the MHM6- population is augmented three- to sixfold by the addition of mitomycin C (MC)-treated MHM6+ cells. Pretreatment of cells with anti-leukocyte functional antigen 1 mAb has little effect on the subsequent proliferation of the MHM6- population but shows cell contact to be critical for the proliferation of MHM6+ cells. Such pretreatment has revealed that the functional interaction observed between MHM6+ and MHM6- cells is dependent on both cell contact and the presence of an MHM6+ cell-derived soluble component. We have found that addition of soluble CD23, purified from Epstein-Barr virus-transformed lymphoblastoid cell line supernatant, increases the proliferative response of MHM6- tonsil B cells to mitogenic stimuli in the presence of inactivated MHM6+ cells but has no effect on proliferation when MHM6+ cells are absent. By way of contrast to normal B lymphocytes, we have examined functional responses of prolymphocytic leukemia (PLL) B cells. Although these cells, when freshly isolated, show comparable levels of CD23 expression to normal B cells, this expression is not increased upon activation. In addition, in contrast to normal B cells, the PLL MHM6- population cultured alone shows a strong proliferative response to various mitogenic stimuli, comparable to that of mHM6+ or unfractionated cells, and this response is not augmented by the addition of MC-treated MHM6+ cells. Thus, a novel functional interaction is described between normal, but not leukemic, B cell populations defined by their expression of CD23. This interaction involves two components, one mediated through cell contact and the other by the presence of soluble factor(s) derived from the MHM6+ cells with neither component alone being effective.