Cook R G, Stavitsky A B, Schoenberg M D
J Immunol. 1975 Jan;114(1 Pt 2):426-34.
Keyhole limpet hemocyanin was injected into the hind foot pads of rabbits. Six days later cell suspensions were prepared from the popliteal lymph nodes. Various amounts of hemocyanin (1 ng to 100 mug) were added to 1 times 10-7 cells to induce an anamnestic antibody response. Various amounts of cholera enterotoxin, which stimulates the enzyme adenylate cyclase, or dibutyryl cyclic adenosine 3'5'-monophosphate (AMP), were added to the cultures with or without hemocyanin. De novo synthesis of antibody, protein, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from radioactive precursors was assayed. The addition of cholera toxin or dibutyryl cyclic AMP for the first 24 hr with optimal (1 mug) or supraoptimal (100 mug) amounts of hemocyanin enhanced antibody synthesis by at least 100 to 200%. Addition of the toxin or dibutyryl cyclic AMP for the same period to cells minus hemocyanin or with suboptimal amounts (1 to 100 ng) of antigen failed to enhance antibody synthesis. Addition of these agents for 72 to 120 hr to hemocyanin-induced cultures consistently inhibited antibody synthesis. These agents slightly inhibited DNA and RNA synthesis. The increase in protein synthesis caused by the toxin or dibutyryl cyclic AMP was almost totally accounted for by the increase in antibody synthesis. Neither toxin nor cyclic nucleotide promoted the antibody response in the presence of antibody to rabbit thymus-derived lymphocytes; these lymphocytes as well as bursa-equivalent lymphocytes were required for potentiation of the response. Macrophages were not required either for induction of the anamnestic response or for enhancement of this synthesis by cyclic nucleotide or cholera toxin. Both IgM and IgG antibody synthesis were regulated by exogenous cholera toxin and dibutyryl cyclic AMP. A number of possible cellular mechanisms of regulation of the antibody response through the cyclic AMP pathway were discussed. These included the effects of modifications of this pathway on the activities of T lymphocytes early (0 to 24 hr) and B lymphocytes late (72 to 120 hr) in the response and on the apparent reversal of high zone tolerance.
将钥孔戚血蓝蛋白注射到兔子的后足垫中。6天后，从腘窝淋巴结制备细胞悬液。将不同量的血蓝蛋白（1纳克至100微克）添加到1×10⁻⁷个细胞中，以诱导回忆性抗体反应。将不同量的刺激酶腺苷酸环化酶的霍乱肠毒素或二丁酰环腺苷3',5'-单磷酸（AMP）添加到含有或不含有血蓝蛋白的培养物中。测定了从放射性前体从头合成抗体、蛋白质、脱氧核糖核酸（DNA）和核糖核酸（RNA）的情况。在最初24小时内，加入霍乱毒素或二丁酰环AMP以及最佳量（1微克）或超最佳量（100微克）的血蓝蛋白可使抗体合成增强至少100%至200%。在相同时间段内，将毒素或二丁酰环AMP添加到不含血蓝蛋白或含有次最佳量（1至100纳克）抗原的细胞中，未能增强抗体合成。将这些试剂添加到血蓝蛋白诱导的培养物中72至120小时，持续抑制抗体合成。这些试剂轻微抑制DNA和RNA合成。毒素或二丁酰环AMP引起的蛋白质合成增加几乎完全由抗体合成增加所导致。在存在针对兔胸腺来源淋巴细胞的抗体时，毒素和环核苷酸均未促进抗体反应；这种反应的增强需要这些淋巴细胞以及类囊淋巴细胞。无论是诱导回忆性反应还是通过环核苷酸或霍乱毒素增强这种合成，都不需要巨噬细胞。IgM和IgG抗体合成均受外源性霍乱毒素和二丁酰环AMP调节。讨论了通过环AMP途径调节抗体反应的一些可能的细胞机制。这些机制包括该途径的修饰对反应早期（0至24小时）T淋巴细胞和晚期（72至120小时）B淋巴细胞活性的影响以及对高区耐受性明显逆转的影响。
