Brändlein Stephanie, Pohle Tina, Ruoff Nele, Wozniak Ewa, Müller-Hermelink Hans-Konrad, Vollmers H Peter
Institute of Pathology, University of Würzburg, Josef-Schneider Strasse 2, D-97080 Würzburg, Germany.
Cancer Res. 2003 Nov 15;63(22):7995-8005.
Malignancy is like a chronic disease, and the immune system is permanently involved in recognizing and eliminating the transformed cells. The human hybridoma technology offers the unique opportunity to study the mechanisms, structures, and targets involved in recognition and elimination of aberrant cells. Thousands of tumor-reactive human monoclonal antibodies were isolated by this technique from cancer patients and from healthy donors, and all of these antibodies were IgM antibodies; no IgG and IgA antibodies were found. Fourteen of these antibodies were selected for DNA sequence analysis, characterization of their binding patterns, and determination of their origin and genetics. All of the IgM antibodies studied expressed only few or no mutations at all (germ-line coded), bound to carbohydrates on modified tumor-specific receptors and induced apoptosis. The degree of cross-reactivity to other tumors correlated reciprocally with the number of mutations in coding regions. By using an anti-idiotypic antibody we were able to show that the IgM-producing cells were of CD5+ B-cell origin. The data presented here indicate that the innate immunity and natural IgM antibodies play an important role in immunosurveillance mechanisms against epithelial tumors in humans.
恶性肿瘤就像一种慢性疾病，免疫系统始终参与识别和清除转化细胞。人类杂交瘤技术为研究识别和清除异常细胞所涉及的机制、结构及靶点提供了独特的机会。通过该技术从癌症患者和健康供体中分离出了数千种肿瘤反应性人单克隆抗体，所有这些抗体均为IgM抗体；未发现IgG和IgA抗体。选择其中14种抗体进行DNA序列分析、结合模式表征以及起源和遗传学测定。所有研究的IgM抗体仅表达很少的突变或根本不表达突变（种系编码），与修饰的肿瘤特异性受体上的碳水化合物结合并诱导细胞凋亡。与其他肿瘤的交叉反应程度与编码区的突变数量呈反比。通过使用抗独特型抗体，我们能够证明产生IgM的细胞起源于CD5 + B细胞。此处呈现的数据表明，先天免疫和天然IgM抗体在人类针对上皮肿瘤的免疫监视机制中发挥重要作用。
