Beauvais F, Hieblot C, Burtin C, Benveniste J
INSERM U.200, Université Paris-sud, Clamart, France.
J Immunol. 1990 May 15;144(10):3881-90.
The role of IgG4 antibodies in allergic disorders is suspected. Yet, their presence on human basophil membrane has not been demonstrated and the mechanism of the degranulation induced by anti-IgG4 antibodies remains unclear. As previously reported, we observed that monoclonal anti-IgG4 (10 to 100 micrograms/ml) induced histamine release in the presence of D2O from leukocytes of normal and atopic subjects. The release was accompanied by a decrease of the number of toluidine blue-positive basophils (TB+). Histamine release and TB+ decrease were also observed with lower concentrations of anti-IgG4 (1 to 100 pg/ml). Since basophil activation assessed by TB+ decrease was more sensitive than histamine release, we thus used the former method to further study the mechanisms of the anti-IgG4- vs anti-IgE-induced basophil activation. Basophil activation by anti-IgG4 at 1 to 100 pg/ml, but not by anti-IgG4 at 10 to 100 micrograms/ml or anti-IgE, required the presence of polymorphonuclear cells. Furthermore, anti-IgG4-stimulated purified eosinophils, but not neutrophils, released basophil-activating factors identified as cationic proteins from eosinophils. Thus, the human basophil can be activated by anti-IgG4 via two different mechanisms according to the antibody concentration. At high concentrations (10 to 100 micrograms/ml) basophil activation does not require the presence of polymorphonuclear cells whereas at lower concentrations (1 to 100 pg/ml) the presence of eosinophils is necessary. We propose that in the latter concentration range, basophil activation is a two-step process: 1) release by anti-IgG4 of eosinophil cationic proteins that 2) will, in turn, activate human basophils. This study lends support to the role of IgG4 and eosinophils in anaphylactic reactions.
IgG4抗体在过敏性疾病中的作用受到怀疑。然而，它们在人嗜碱性粒细胞膜上的存在尚未得到证实，并且抗IgG4抗体诱导脱颗粒的机制仍不清楚。如先前报道，我们观察到单克隆抗IgG4（10至100微克/毫升）在重水存在下可诱导正常和特应性受试者白细胞释放组胺。释放过程伴随着甲苯胺蓝阳性嗜碱性粒细胞（TB+）数量的减少。在较低浓度的抗IgG4（1至100皮克/毫升）下也观察到组胺释放和TB+减少。由于通过TB+减少评估的嗜碱性粒细胞活化比组胺释放更敏感，因此我们使用前一种方法进一步研究抗IgG4与抗IgE诱导的嗜碱性粒细胞活化机制。1至100皮克/毫升的抗IgG4可激活嗜碱性粒细胞，但10至100微克/毫升的抗IgG4或抗IgE则不能，这需要多形核细胞的存在。此外，抗IgG4刺激纯化的嗜酸性粒细胞而非中性粒细胞释放被鉴定为嗜酸性粒细胞阳离子蛋白的嗜碱性粒细胞活化因子。因此，根据抗体浓度，人嗜碱性粒细胞可通过两种不同机制被抗IgG4激活。在高浓度（10至100微克/毫升）下，嗜碱性粒细胞活化不需要多形核细胞的存在，而在较低浓度（1至100皮克/毫升）下，嗜酸性粒细胞的存在是必要的。我们提出，在后一浓度范围内，嗜碱性粒细胞活化是一个两步过程：1）抗IgG4释放嗜酸性粒细胞阳离子蛋白，2）这些蛋白进而激活人嗜碱性粒细胞。本研究支持了IgG4和嗜酸性粒细胞在过敏反应中的作用。
