Abu-hadid M M, Bankert R B, Mayers G L
Department of Microbiology, State University of New York at Buffalo 14214.
Proc Natl Acad Sci U S A. 1987 Oct;84(20):7232-6. doi: 10.1073/pnas.84.20.7232.
The administration of dextran-conjugated cytosine arabinonucleoside (araC) to BALB/c mice at various times prior to but not subsequent to immunization with native dextran renders mice unresponsive to this thymic-independent antigen. These results demonstrate that the primary immune response to an antigen can be selectively and efficiently suppressed or eliminated in vivo by the delivery of a single dose of an appropriate antigen-cytotoxic drug conjugate. Evidence presented here indicates that the dextran-araC conjugate (toxogen) acts directly and selectively upon unprimed dextran-specific antibody-forming cell precursors, presumably by binding to their receptors and subsequent internalization of the resultant receptor-toxogen complexes. The resistance of antigen-primed mice to the cytotoxic effect of the toxogen could result from the failure of dextran-primed cells to reexpress antigen-specific receptors, from an alternative processing of the toxogen, or from the inability of the antigen-primed cells to internalize a second round of receptor-ligand complexes. We also determined that B cells responding to thymic-dependent antigens were not affected by the prior exposure to a toxogen. The inability to eliminate or suppress the primary response to a thymic-dependent antigen via the administration of a cytotoxic drug-antigen conjugate distinguishes the thymic-independent set of B cells from the thymic-dependent B-cell repertoire. The difference between these two B-cell compartments could be due either to differences in the amount of ligand bound to receptors or to differences in the trafficking patterns of receptor-ligand complexes within each cell type.
在给BALB/c小鼠用天然葡聚糖免疫之前而非之后的不同时间给予葡聚糖偶联的阿糖胞苷（araC），会使小鼠对这种非胸腺依赖性抗原无反应。这些结果表明，通过单次给予适当的抗原 - 细胞毒性药物偶联物，可在体内选择性且有效地抑制或消除对抗原的初次免疫反应。此处提供的证据表明，葡聚糖 - araC偶联物（毒素原）可能通过与未致敏的葡聚糖特异性抗体形成细胞前体的受体结合并随后内化形成的受体 - 毒素原复合物，直接且选择性地作用于这些细胞前体。抗原致敏小鼠对毒素原细胞毒性作用的抗性可能源于葡聚糖致敏细胞无法重新表达抗原特异性受体、毒素原的另一种加工方式，或者抗原致敏细胞无法内化第二轮受体 - 配体复合物。我们还确定，对胸腺依赖性抗原作出反应的B细胞不受先前接触毒素原的影响。通过给予细胞毒性药物 - 抗原偶联物无法消除或抑制对胸腺依赖性抗原的初次反应，这将非胸腺依赖性B细胞组与胸腺依赖性B细胞库区分开来。这两个B细胞区室之间的差异可能是由于与受体结合的配体数量不同，或者是由于每种细胞类型内受体 - 配体复合物的运输模式不同。
