Minota S, Winfield J B
Division of Rheumatology and Immunology, University of North Carolina at Chapel Hill 27514.
J Immunol. 1987 Dec 1;139(11):3644-51.
Three cell lymphocyte antigens of m.w. 55,000, 70,000, and 105,000 to 110,000 were identified by Western blotting as targets of IgM autoantibodies in serum from a group of 49 patients with systemic lupus erythematosus. The 55- and 70-kDa antigens were well expressed on unstimulated peripheral T cells, whereas the 105- to 110-kDa target was demonstrable only on mitogen-activated T cells and lymphoblastoid T cell lines. Localization of these molecules to the plasma membrane was established by cytoabsorption experiments in which IgM antibody staining of blotted antigens was specifically absorbed from systemic lupus erythematosus serum during 4 degrees C incubations with intact lymphocytes, and by their detection in purified lymphocyte plasma membranes. While the identity of these target antigens vis a vis known surface determinants was not defined, their expression on peripheral T cells from multiple donors and on cell lines of both undifferentiated (HSB-2) and phenotypically mature (Jurkat; HUT 78) types excluded alloantigens, major histocompatibility complex-encoded determinants, and most T cell differentiation antigens as candidates in this regard. Expression of the IgM autoantibody targets on HSB-2 cells argues against discrete T subset specificities as well. IgM reactivity with the 55-, 70-, and 105- to 110-kDa antigens by blotting was highly correlated with antilymphocyte antibody activity in complement-dependent cytotoxicity assays (Fisher's p less than 0.001), and paralleled flow microfluorimetric and microcytotoxicity quantitation of IgM antibody activity in serial observations of individual patients studied during different phases of disease activity. Taken together, these data suggest that IgM lymphocytotoxic antibodies in systemic lupus erythematosus are directed predominantly against a limited number of non-T cell subset-specific antigens.
通过蛋白质印迹法，在49例系统性红斑狼疮患者的血清中，鉴定出分子量分别为55,000、70,000以及105,000至110,000的三种细胞淋巴细胞抗原，它们是IgM自身抗体的靶标。55 kDa和70 kDa的抗原在未受刺激的外周T细胞上表达良好，而105至110 kDa的靶标仅在有丝分裂原激活的T细胞和淋巴母细胞样T细胞系上可检测到。通过细胞吸附实验确定了这些分子定位于质膜，在该实验中，在4℃与完整淋巴细胞孵育期间，系统性红斑狼疮血清中印迹抗原的IgM抗体染色被特异性吸附，并且通过在纯化的淋巴细胞质膜中检测到它们得以证实。虽然这些靶抗原与已知表面决定簇的身份尚未明确，但它们在多个供体的外周T细胞以及未分化（HSB-2）和表型成熟（Jurkat；HUT 78）类型的细胞系上的表达排除了同种抗原、主要组织相容性复合体编码的决定簇以及在这方面作为候选物的大多数T细胞分化抗原。IgM自身抗体靶标在HSB-2细胞上的表达也排除了离散的T亚群特异性。通过印迹法检测到的IgM与55 kDa、70 kDa以及105至110 kDa抗原的反应性与补体依赖性细胞毒性试验中的抗淋巴细胞抗体活性高度相关（Fisher检验p小于0.001），并且在对处于疾病活动不同阶段的个体患者进行的系列观察中，与IgM抗体活性的流式微荧光测定和微细胞毒性定量结果平行。综上所述，这些数据表明系统性红斑狼疮中的IgM淋巴细胞毒性抗体主要针对有限数量的非T细胞亚群特异性抗原。
