Isobe K I, Nakashima I, Nagase F, Kato N, Mizoguchi K, Kawashima K, Lake P
J Immunol. 1984 Mar;132(3):1100-5.
Thy-1 antigens are the only cell membrane antigens known to be able to induce primary antibody responses in vitro. We have shown that antigens from the thymocytes of mice and rats were highly immunogenic in cultures of murine spleen cells for the induction of Thy-1.1-specific plaque-forming cell responses, whereas antigens from other tissues, including brains and bone marrow, were poorly immunogenic, if at all. The thymocyte-specific Thy-1 immunogenicity was carried by disrupted cell membranes, and the specific activity for inducing responses was closely linked to Thy-1. We then tried to determine the mechanism of anti-Thy-1 antibody responses in vitro that were induced by the uniquely immunogenic thymocyte antigens. The thymocyte Thy-1 antigens behaved as T cell-independent class 2 (TI-2) antigens: they induced responses in athymic nude mice but not in CBA/N mice with a B cell defect. The apparent TI-2 responses to thymocyte Thy-1 did, however, require Thy-1+ cells in the responder, similar to anti-DNP-Ficoll responses. The full development of the anti-Thy-1 responses required the participation of splenic adherent cells (SAC). Nevertheless, the mechanism of the SAC dependency of anti-Thy-1 responses did not involve antigen presentation to lymphocytes by antigen-pulsed SAC, which contrasted with the finding that the presentation of antigen by live SAC to lymphocytes was indispensable for responses to DNP-Ficoll. The poor Thy-1 responsiveness of SAC-depleted spleen cells was fully restored by the addition of soluble factors (IL 1-like molecules) released from SAC into the culture, which did not replace the SAC-requirement of responses to DNP-Ficoll. It was concluded from these results that Thy-1 or Thy-1-linked structures on thymocyte membranes have an intrinsic activity to directly signal either TI-2 B cells or immature T cells, or both, for activation in the presence of soluble factors released from adherent accessory cells. This conclusion is discussed in relation to a hypothetical view that the thymocyte Thy-1 would physiologically mediate cell-to-cell interactions among special subsets of lymphocytes under thymic influence.
Thy-1抗原是已知唯一能够在体外诱导初次抗体应答的细胞膜抗原。我们已经表明，来自小鼠和大鼠胸腺细胞的抗原在鼠脾细胞培养物中具有高度免疫原性，可诱导Thy-1.1特异性空斑形成细胞应答，而来自包括脑和骨髓在内的其他组织的抗原，即使有免疫原性也很差。胸腺细胞特异性的Thy-1免疫原性由破碎的细胞膜携带，诱导应答的比活性与Thy-1密切相关。然后我们试图确定由独特免疫原性的胸腺细胞抗原在体外诱导的抗Thy-1抗体应答的机制。胸腺细胞Thy-1抗原表现为非T细胞依赖性2类（TI-2）抗原：它们能在无胸腺裸鼠中诱导应答，但不能在有B细胞缺陷的CBA/N小鼠中诱导应答。然而，对胸腺细胞Thy-1的明显TI-2应答确实需要应答细胞中有Thy-1⁺细胞，这与抗DNP-菲可龙应答相似。抗Thy-1应答的充分发展需要脾黏附细胞（SAC）的参与。然而，抗Thy-1应答对SAC的依赖性机制并不涉及抗原脉冲化的SAC向淋巴细胞呈递抗原，这与活SAC向淋巴细胞呈递抗原是对DNP-菲可龙应答所必需的这一发现形成对比。通过向培养物中添加从SAC释放的可溶性因子（IL-1样分子），可完全恢复SAC耗尽的脾细胞较差的Thy-1应答能力，而这并不能替代对DNP-菲可龙应答中对SAC的需求。从这些结果得出的结论是，胸腺细胞膜上的Thy-1或与Thy-1相关的结构具有内在活性，可在存在来自黏附辅助细胞释放的可溶性因子的情况下，直接向TI-2 B细胞或未成熟T细胞或两者发出信号以激活它们。结合一个假设观点对这一结论进行了讨论，该假设观点认为胸腺细胞Thy-1在胸腺影响下将在淋巴细胞的特殊亚群之间生理介导细胞间相互作用。
