Kuwano K, Arai S, Munakata T, Tomita Y, Yoshitake Y, Kumagai K
J Immunol. 1986 Sep 1;137(5):1462-8.
The suppressive effect of human natural killer (NK) cells on Epstein-Barr virus (EBV)-induced immunoglobulin (Ig) synthesis by autologous B cells was investigated. By Percoll discontinuous density gradient centrifugation, low-density fractions enriched for NK cells were isolated from human peripheral blood lymphocytes. These NK-enriched fractions were added to purified autologous B cells in the presence of EBV, were cultivated for 8 days, and were examined for their suppressive effect on Ig synthesis by an enzyme-linked immunosorbent assay. The fractions markedly suppressed both IgM and IgG synthesis induced by EBV. It was possible to reduce the suppressive effect of NK-enriched cells by complement-dependent lysis of NK cells and Leu-11, but not by OKT3 monoclonal antibody, indicating that NK cells may be responsible for the suppression of Ig synthesis. Upon close examination of interferon (IFN) activity, it was revealed that the co-cultures of NK-enriched cells and EBV-infected B cells generated production of IFN-alpha, which might be produced by NK cells in response to EBV-stimulated B cells. Addition of anti-IFN-alpha but not anti-IFN-gamma serum almost completely abrogated the suppressive effect of NK-enriched cells on Ig synthesis, indicating that IFN-alpha produced are required for the NK cell-mediated suppression of Ig synthesis. However, addition of IFN-alpha into purified B cells showed no direct suppressive effect on EBV-induced Ig synthesis by B cells in the absence of NK cells. Nevertheless, NK cells when previously incubated with IFN-alpha and added to B cells showed a suppressor activity on Ig synthesis to a level higher than that of untreated NK controls. These results strongly suggest the possibility that NK cells display an interaction with EBV-infected B cells and produce IFN-alpha, which in turn activates NK cells. These activated NK cells suppress the Ig synthesis by B cells, which undergo transformation induced by EBV.
研究了人类自然杀伤（NK）细胞对爱泼斯坦 - 巴尔病毒（EBV）诱导的自体B细胞免疫球蛋白（Ig）合成的抑制作用。通过Percoll不连续密度梯度离心法，从人外周血淋巴细胞中分离出富含NK细胞的低密度组分。将这些富含NK细胞的组分在EBV存在下加入纯化的自体B细胞中，培养8天，并通过酶联免疫吸附测定法检测其对Ig合成的抑制作用。这些组分显著抑制了EBV诱导的IgM和IgG合成。通过NK细胞和Leu - 11的补体依赖性裂解可以降低富含NK细胞的抑制作用，但OKT3单克隆抗体不能，这表明NK细胞可能是Ig合成抑制的原因。仔细检查干扰素（IFN）活性后发现，富含NK细胞的细胞与EBV感染的B细胞共培养产生了IFN - α，这可能是NK细胞对EBV刺激的B细胞作出反应而产生的。加入抗IFN - α血清而非抗IFN - γ血清几乎完全消除了富含NK细胞的组分对Ig合成的抑制作用，表明产生的IFN - α是NK细胞介导的Ig合成抑制所必需的。然而，在没有NK细胞的情况下，将IFN - α加入纯化的B细胞中对EBV诱导的B细胞Ig合成没有直接抑制作用。尽管如此，预先用IFN - α孵育并加入B细胞的NK细胞对Ig合成的抑制活性高于未处理的NK对照。这些结果强烈提示NK细胞与EBV感染的B细胞存在相互作用并产生IFN - α，进而激活NK细胞的可能性。这些活化的NK细胞抑制了由EBV诱导发生转化的B细胞的Ig合成。
