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人源单克隆IgG1和IgM抗体针对B族链球菌的调理素及补体激活活性比较

Comparison of the opsonic and complement triggering activity of human monoclonal IgG1 and IgM antibody against group B streptococci.

作者信息

Shyur S D, Raff H V, Bohnsack J F, Kelsey D K, Hill H R

机构信息

Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132.

出版信息

J Immunol. 1992 Mar 15;148(6):1879-84.

PMID:1541826
Abstract

We have compared the opsonic and complement-triggering activity of transfectoma-derived, class-switched human IgG1 and IgM mAb (HumAb) against types Ia, II and III group B streptococci (GBS). These antibodies appear to be directed against the common group B cell wall Ag of these organisms. The HumAb IgM promotes uptake of type Ia and II GBS at concentrations as low as 37 ng/ml and type III GBS at concentrations of 150 ng/ml in the presence of human neonatal complement. In contrast, the IgG1 GBS HumAB showed no detectable opsonic activity in concentrations up to 600 ng/ml. When the concentration of HumAb IgG1 is raised to 2.5 micrograms/ml, significant opsonic activity against GBS is detected and when the concentration is approximately 40 micrograms/ml, the opsonic activity peaked at a slightly higher level than that with the HumAb IgM. Thus, approximately 100- fold higher concentrations of the IgG1 than the IgM HumAb are required for optimal opsonization. The opsonic activity of the IgM and IgG1 HumAb are closely related to their ability to consume complement and deposit C3 on the surface of type Ia, II, and III GBS (r = 0.959). We believe that the marked opsonic and protective activity of the IgM GBS HumAb is due to its enhanced avidity and ability to trigger the complement system. Further studies are indicated to determine the feasibility of employing human IgM antibody preparations in the immunotherapy of neonatal GBS disease.

摘要

我们比较了转染瘤衍生的、类别转换的人IgG1和IgM单克隆抗体(HumAb)对Ia、II和III型B族链球菌(GBS)的调理吞噬和补体激活活性。这些抗体似乎针对这些细菌的共同B族细胞壁抗原。在人新生儿补体存在的情况下,HumAb IgM在低至37 ng/ml的浓度下促进Ia型和II型GBS的摄取,在150 ng/ml的浓度下促进III型GBS的摄取。相比之下,IgG1 GBS HumAB在高达600 ng/ml的浓度下未检测到可检测的调理吞噬活性。当HumAb IgG1的浓度提高到2.5μg/ml时,检测到对GBS的显著调理吞噬活性,当浓度约为40μg/ml时,调理吞噬活性达到峰值,略高于HumAb IgM。因此,最佳调理吞噬作用所需的IgG1浓度比IgM HumAb高约100倍。IgM和IgG1 HumAb的调理吞噬活性与其消耗补体并在Ia、II和III型GBS表面沉积C3的能力密切相关(r = 0.959)。我们认为,IgM GBS HumAb显著的调理吞噬和保护活性归因于其增强的亲和力和触发补体系统的能力。需要进一步研究以确定在新生儿GBS疾病免疫治疗中使用人IgM抗体制剂的可行性。

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