Allebes W A, Wetzels R H, Capel P J
Department of Nephrology, University Hospital, Nijmegen, The Netherlands.
Scand J Immunol. 1988 Jul;28(1):95-103. doi: 10.1111/j.1365-3083.1988.tb02420.x.
Anti-Ig antibodies can have two opposing effects on B-cell proliferation, resulting either in stimulation or inhibition. We have examined the proliferative response of 30 B-cell tumours to anti-Ig in the presence and absence of B-cell growth factor. Three reaction patterns were observed. In 12 cases a dose-dependent synergism between anti-Ig and B-cell growth factor was present in the induction of proliferation, in ten cases anti-Ig did not induce any response, and in eight cases anti-Ig suppressed the B-cell growth factor (BCGF)-induced proliferation. Similar responses to anti-Ig were found in the absence of BCGF. When these B-cell tumours were typed for expression of Ig isotypes, HLA class II antigens, several B-cell markers, activation markers, complement receptors, Fc receptors, cell size, and cell cycle phase, no correlation could be found with the proliferative response of these tumour B cells to anti-Ig. T cells or T-cell factors were not involved, because T-cell depletion did not change the tumour B-cell proliferative response to incubation with anti-Ig. The observed inhibition of proliferation did not correlate with the expression of Fc receptors, indicating the involvement of suppressor mechanisms other than the cross-linking of Fc receptors with surface immunoglobulins. Tumour B cells, for which monoclonal anti-idiotypic antibodies (MoAb anti-id) were available, responded to MoAb anti-id in the same way as they did to anti-Ig. In view of the treatment of B-cell malignancies with MoAb anti-id, the question of whether these responses in vitro correlate with in vivo clinical outcome of anti-id therapy is of interest. So far our data show that the proliferative response of B-cell tumours to anti-Ig or MoAb anti-id is heterogeneous and cannot be linked to phenotype, is T cell-independent, and is most likely an intrinsic property of the malignant cell.
抗 Ig 抗体对 B 细胞增殖可产生两种相反的作用，即刺激或抑制。我们研究了 30 个 B 细胞肿瘤在有和无 B 细胞生长因子存在的情况下对抗 Ig 的增殖反应。观察到三种反应模式。12 例中，抗 Ig 与 B 细胞生长因子在诱导增殖方面存在剂量依赖性协同作用；10 例中，抗 Ig 未诱导任何反应；8 例中，抗 Ig 抑制了 B 细胞生长因子（BCGF）诱导的增殖。在无 BCGF 的情况下也发现了对抗 Ig 的类似反应。当对这些 B 细胞肿瘤进行 Ig 同种型、HLA Ⅱ类抗原、几种 B 细胞标志物、激活标志物、补体受体、Fc 受体、细胞大小和细胞周期阶段的表达分型时发现，这些肿瘤 B 细胞对抗 Ig 的增殖反应与之无相关性。T 细胞或 T 细胞因子未参与其中，因为 T 细胞耗竭并未改变肿瘤 B 细胞与抗 Ig 孵育后的增殖反应。观察到的增殖抑制与 Fc 受体的表达无关，这表明除了 Fc 受体与表面免疫球蛋白交联之外，还涉及其他抑制机制。对于有单克隆抗独特型抗体（MoAb 抗 -id）的肿瘤 B 细胞，它们对 MoAb 抗 -id 的反应与对抗 Ig 的反应相同。鉴于用 MoAb 抗 -id 治疗 B 细胞恶性肿瘤，这些体外反应是否与抗独特型治疗的体内临床结果相关这一问题备受关注。到目前为止，我们的数据表明，B 细胞肿瘤对抗 Ig 或 MoAb 抗 -id 的增殖反应是异质性的，与表型无关，不依赖 T 细胞，很可能是恶性细胞的固有特性。
