Boue F, Wallon C, Goujard C, Barre-Sinoussi F, Galanaud P, Delfraissy J F
INSERM, U131 Hôpital Antoine Béclère, Clamart, France.
J Immunol. 1992 Jun 15;148(12):3761-7.
In vitro, normal B cells can produce TNF-alpha and IL-6 when activated with a first signal, and cytokines and B lymphocytes from some HIV-infected individuals spontaneously secrete TNF-alpha and IL-6, although the direct involvement of HIV has not been fully explored. In this study, we examined the effects of HIV (purified virus and a recombinant envelope protein) and various IL on TNF-alpha and IL-6 in vitro production by highly purified normal B cells. HIV alone did not induce IL-6 or TNF-alpha production by B cells from healthy subjects. HIV induced IL-6 production (500 to 1500 pg) in the presence of IL-4, with a slight production of TNF-alpha. IL-6 production occurred independently of the presence or absence of TNF-alpha in contrast with Staphylococcus aureus cowan + IL-2-activated B cells. Other IL, particularly IL-2, were unable to induce IL-6 secretion by HIV-activated B cells. In vivo-activated B cells from HIV-infected patients spontaneously produce moderate quantities of IL-6 and TNF-alpha. This secretion was markedly increased by HIV, suggesting that IL-6-secreting B cells contain anti-HIV antibody-producing B cells. However, contrary to normal B cells, IL-6 production by B cells from HIV-infected patients was not further enhanced by IL-4. Then HIV itself is able to induce an autocrine production of IL-6 upon interaction with IL-4, which can contribute to the hypergammaglobulinemia and to the global B cell dysfunction observed in HIV-infected patients.
在体外，正常B细胞在接受第一信号激活时可产生肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6），一些HIV感染个体的细胞因子和B淋巴细胞可自发分泌TNF-α和IL-6，尽管HIV的直接作用尚未得到充分研究。在本研究中，我们检测了HIV（纯化病毒和重组包膜蛋白）以及各种白细胞介素对高度纯化的正常B细胞体外产生TNF-α和IL-6的影响。单独的HIV不会诱导健康受试者的B细胞产生IL-6或TNF-α。在IL-4存在的情况下，HIV可诱导IL-6产生（500至1500皮克），同时伴有少量TNF-α产生。与金黄色葡萄球菌考恩株+IL-2激活的B细胞不同，IL-6的产生与TNF-α的有无无关。其他白细胞介素，尤其是IL-2，无法诱导HIV激活的B细胞分泌IL-6。来自HIV感染患者的体内激活B细胞可自发产生适量的IL-6和TNF-α。HIV可显著增加这种分泌，提示分泌IL-6的B细胞包含产生抗HIV抗体的B细胞。然而，与正常B细胞相反，IL-4不会进一步增强HIV感染患者的B细胞产生IL-6的能力。因此，HIV自身在与IL-4相互作用时能够诱导IL-6的自分泌产生，这可能导致HIV感染患者出现高球蛋白血症和整体B细胞功能障碍。
