REGULATION OF MURINE INVIVO IGG AND IGE RESPONSES BY A MONOCLONAL ANTI-IL-4 RECEPTOR ANTIBODY
REGULATION OF MURINE INVIVO IGG AND IGE RESPONSES BY A MONOCLONAL ANTI-IL-4 RECEPTOR ANTIBODY
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DOI：
10.1093/intimm/3.6.599
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发表时间：
1991-06-01
影响因子：
4.4
通讯作者：
KATONA, IM
中科院分区：
文献类型：
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作者：
FINKELMAN, FD;URBAN, JF;KATONA, IM
虽然细胞因子白介素4 （IL-4）刺激lps激活的小鼠B淋巴细胞分泌IgG1和IgE，但抗IL-4抗体完全抑制IgE反应，但对几种体内IgG反应几乎没有或没有影响。因此，IL-4可能在体内体液免疫反应的产生中具有有限的作用。或者，IgG1反应可能是由直接与B细胞相互作用的T细胞分泌的IL-4刺激的，因此抗IL-4抗体在与B细胞IL-4受体结合之前不能中和IL-4。相反，阻断IL-4受体（IL-4R）的抗体应该同样抑制对近端或远端B细胞产生的IL-4的反应。这一推理使我们确定了抗il - 4r单抗能否影响小鼠注射山羊抗小鼠IgD抗体（GaM-delta）或接种多回Heligmosomoides线虫寄生虫的抗体产生。Anti-IL-4R mAb与anti-IL-4 mAb一样，阻断了95%的IgE应答，并在不同程度上增强了IgG2a应答。然而，抗il - 4r单抗对诱导IgG1反应只有适度和可变的抑制作用，尽管它使这些反应更快地终止。抗il -4和抗il - 4r单抗联合使用完全阻断山羊抗小鼠IgD抗体（GaM-delta）诱导的IgE产生，但对IgG1的产生无加性抑制作用。这些观察结果与IL-4是原发性IgE反应所必需的观点最为一致，但在研究的体内系统中，IL-4在诱导IgG1反应方面的作用相对较小。
Although the cytokine interleukin 4 (IL-4) stimulates LPS-activated mouse B lymphocytes to secrete both IgG1 and IgE, an anti-IL-4 antibody completely inhibits IgE responses but has little or no effect on several in vivo IgG responses. IL-4 might, therefore, have a restricted role in the generation of in vivo humoral immune responses. Alternatively, IgG1 responses might be stimulated by IL-4 secreted by T cells that are interacting directly with B cells, so that anti-IL-4 antibody cannot neutralize IL-4 before it binds to a B cell IL-4 receptor. In contrast, an antibody that blocks the IL-4 receptor (IL-4R) should equally inhibit responses to IL-4 produced proximal to or distant from a B cell. This reasoning led us to determine the ability of an anti-IL-4R mAb to affect antibody production in mice injected with a goat antibody to mouse IgD (GaM-delta) or inoculated with the nematode parasite Heligmosomoides polygyrus. Anti-IL-4R mAb, like anti-IL-4 mAb, blocked IgE responses by > 95% and enhanced IgG2a responses to a variable extent. Anti-IL-4R mAb, however, had only a modest and variable inhibitory effect on the induction of IgG1 responses, although it caused these responses to terminate more rapidly. A combination of anti-IL-4 and anti-IL-4R mAbs totally blocked goat anti-mouse IgD antibody (GaM-delta)-induced IgE production but had no additive inhibitory effect on IgG1 production. These observations are most consistent with the view that IL-4 is required for a primary IgE response, but has relatively little role in the induction of IgG1 responses in the in vivo systems studied.