Miller J F, Sprent J, Basten A, Warner N L, Breitner J C, Rowland G, Hamilton J, Silver H, Martin W J
J Exp Med. 1971 Nov 1;134(5):1266-84. doi: 10.1084/jem.134.5.1266.
Experiments were designed to test the possibility that thymus-derived (T) cells cooperate with nonthymus derived (B) cells in antibody responses by acting as passive carriers of antigen. Thoracic duct lymphocytes (TDL) from fowl gammaG-tolerant mice were incubated in vitro with fowl anti-mouse lymphocyte globulin (FALG), which was shown not to be immunosuppressive in mice. On transfer into adult thymectomized, irradiated, and marrow protected (TxBM) hosts together with a control antigen, horse RBC, a response to horse RBC but not to fowl gammaG was obtained. By contrast, TxBM recipients of nontolerant, FALG-coated TDL responded to both antigens and the antibody-forming cells were shown to be derived from the host, not from the injected TDL. These findings suggested that, under the conditions of the experiment, triggering of unprimed B cells in the spleens of TxBM hosts was not achieved with antigen-coated tolerant lymphocytes. Another model utilized the ability of B cells to bind antibody-antigen complexes. Spleen cells from TxBM mice, incubated in vitro with anti-fowl gammaG-fowl gammaG.NIP, were injected with or without normal TDL (a source of T cells) into irradiated hosts. Only mice given both cell types could produce an anti-NIP antibody response. In a further experiment, spleen cells from HGG.NIP-primed mice were injected together with NIP-coated B cells (prepared as above) into irradiated hosts. A substantial anti-NIP antibody response occurred. If, however, the T cells in the spleens of HGG.NIP-primed mice were eliminated by treatment with anti-theta serum and complement, the NIP response was abolished. It was concluded that antigen-coated B cells could not substitute for T cells either in the primary or secondary response. Treatment of T cells from unprimed or primed mice with mitomycin C impaired their capacity to collaborate with B cells on transfer into irradiated hosts. Taken together these findings suggest that before collaboration can take place T cells must be activated by antigen to differentiate and in so doing may produce some factor essential for triggering of B cells.
设计实验以测试胸腺来源（T）细胞通过作为抗原的被动载体，在抗体应答中与非胸腺来源（B）细胞协作的可能性。将来自对鸡γG耐受小鼠的胸导管淋巴细胞（TDL）与鸡抗小鼠淋巴细胞球蛋白（FALG）在体外孵育，已证明FALG对小鼠无免疫抑制作用。将其与对照抗原马红细胞一起转移到成年胸腺切除、照射并骨髓保护（TxBM）的宿主中，获得了对马红细胞而非鸡γG的应答。相比之下，接受未耐受、FALG包被的TDL的TxBM受体对两种抗原均有应答，且抗体形成细胞显示来源于宿主，而非注射的TDL。这些发现表明，在实验条件下，用抗原包被的耐受淋巴细胞无法在TxBM宿主的脾脏中触发未致敏的B细胞。另一个模型利用了B细胞结合抗体 - 抗原复合物的能力。将来自TxBM小鼠的脾细胞与抗鸡γG - 鸡γG.NIP在体外孵育，在有或无正常TDL（T细胞来源）的情况下注射到受照射的宿主中。只有同时给予两种细胞类型的小鼠才能产生抗NIP抗体应答。在进一步的实验中，将来自HGG.NIP致敏小鼠的脾细胞与NIP包被的B细胞（如上制备）一起注射到受照射的宿主中。出现了显著的抗NIP抗体应答。然而，如果用抗θ血清和补体处理HGG.NIP致敏小鼠脾脏中的T细胞，NIP应答则被消除。得出的结论是，抗原包被的B细胞在初次或二次应答中均不能替代T细胞。用丝裂霉素C处理未致敏或致敏小鼠的T细胞会损害它们在转移到受照射宿主中时与B细胞协作的能力。综合这些发现表明，在协作发生之前，T细胞必须被抗原激活以进行分化，并且这样做可能会产生一些触发B细胞所必需的因子。
