Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria México D,F C,P, 04510 Mexico City, Mexico.
Cancer Cell Int. 2014 Jan 28;14(1):9. doi: 10.1186/1475-2867-14-9.
Immunosuppression in breast cancer has been reported in women and in the highly metastatic mouse mammary tumor model 4 T1. The immunosuppressive environment complicates the use of the humoral response against the tumor as an immunodiagnostic tool. IgM has not been used in immunodiagnostic in part because its antitumor responses, both innate and adaptive, have not been studied in function of time in breast cancer.We show a new approach to analyzing the mouse humoral immune response, and compare the evolution with time of IgG and IgM responses against the antigens of 4 T1 cells.
The study is based on 2-dimensional immunoblotting detection of antigens from 4 T1 cells by the IgG and IgM antibodies in the serum of female mice injected with 4 T1 cells.
There was a high variability in the intra-and inter-mouse response. Variability in the IgM response was manifested as a pattern of spots that could become a multibinomial variable of 0 and 1, which could represent a signature of the immune response. Different numbers of spots was found in the IgG and IgM responses from week 1 to 5. On average, the IgM had more but the IgG response decrease with the time. The natural IgM at t = 0 responds stronger than w1; the adaptive response of both IgM and IgG were elicited where, with the former being stronger better than the latter. Antigens that are recognized by some female mice in the first week are also recognized by other female mice at time 0. Contamination of the natural IgM makes difficult use the adaptive IgM as a tool for immunodiagnostic.
IgM and IgG response varied with the time and individuals. Spot variation in 2D pattern for the natural IgM could be expressed as a binomial signature, which opens up the way to correlate a particular pattern with resistance or susceptibility. This uncovers a battery of IgMs for each individual to confront cancer or infections. The possibility to differentiate between adaptive IgM antibodies from the natural IgM will allow investigation of the adaptive IgM for early immunodiagnosis.
在乳腺癌患者和高度转移性的小鼠乳腺肿瘤模型 4T1 中均已报道存在免疫抑制。免疫抑制环境使利用针对肿瘤的体液反应作为免疫诊断工具变得复杂。IgM 尚未用于免疫诊断,部分原因是其针对肿瘤的先天和适应性抗肿瘤反应尚未在乳腺癌中进行时间依赖性研究。我们展示了一种分析小鼠体液免疫反应的新方法,并比较了针对 4T1 细胞抗原的 IgG 和 IgM 反应随时间的演变。
该研究基于通过注射了 4T1 细胞的雌性小鼠血清中 IgG 和 IgM 抗体对 4T1 细胞的抗原进行 2 维免疫印迹检测。
小鼠内和小鼠间的反应存在高度变异性。IgM 反应的变异性表现为斑点模式,可以将其视为 0 和 1 的多分类变量,这可能代表免疫反应的特征。在第 1 周到第 5 周之间,在 IgG 和 IgM 反应中发现了不同数量的斑点。平均而言,IgM 的数量更多,但 IgG 反应随时间减少。t=0 时的天然 IgM 反应强度大于 w1;IgM 和 IgG 的适应性反应均被引发,其中前者比后者更强。在第一周被一些雌性小鼠识别的抗原,在第 0 周也被其他雌性小鼠识别。天然 IgM 的污染使得难以将适应性 IgM 用作免疫诊断工具。
IgM 和 IgG 反应随时间和个体而变化。天然 IgM 的 2D 模式中的斑点变化可以表示为二项式特征,这为将特定模式与抵抗或易感性相关联开辟了道路。这为每个个体提供了一组针对癌症或感染的 IgM。区分天然 IgM 与适应性 IgM 抗体的可能性将允许对适应性 IgM 进行早期免疫诊断的研究。