Thyphronitis G, Katona I M, Gause W C, Finkelman F D
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
J Immunol. 1993 Oct 15;151(8):4128-36.
In vitro studies have established that Ig isotype switching typically involves deletion of CH genes that are located between VDJ and the CH gene that will be expressed, and is preceded by transcription of a germline (g) form of that CH gene. Increases in g epsilon transcript levels are induced by the cytokine IL-4, and always precede switching to IgE. To evaluate whether a similar relationship occurs in vivo, we examined IL-4 mRNA, g epsilon RNA, productive (p) epsilon mRNA, and serum IgE levels in two in vivo systems: one in which the injection of anti-IgD antibody induces mIgD+ B cells to switch to the expression of IgE and to secrete this isotype, and a second in which the injection of anti-IgE antibody stimulates IgE secretion by B cells that had been induced to express membrane IgE by earlier treatment with anti-IgD antibody. Increases in IL-4 transcript levels in anti-IgD-injected mice were followed within 24 h by increases in g epsilon RNA, and, one to two days later, by increased p epsilon mRNA and serum IgE levels. IL-4 antagonists blocked the g epsilon and p epsilon RNA and serum IgE responses in these mice, whereas the injection of otherwise untreated mice with IL-4 stimulated, within 24 h, a large increase in g epsilon RNA levels, followed 1-2 days later by a small increase in p epsilon mRNA. Injection of anti-IgD-primed mice with anti-IgE antibody also stimulated increases in IL-4, g epsilon and p epsilon RNA levels; however, the increases in IL-4 and g epsilon RNA were considerably smaller, and the increases in p epsilon mRNA and serum IgE considerably larger, than those observed in anti-IgD antibody-injected mice. IL-4 antagonists blocked the anti-IgE antibody-induced g epsilon RNA response, but not the p epsilon mRNA or serum IgE responses. Thus, IL-4 is required for the induction of g epsilon RNA in at least two in vivo systems, increased g epsilon RNA levels precede increases in p epsilon RNA levels in vivo as in vitro, and neither IL-4 nor g epsilon RNA is required to induce B cells that have already switched to IgE expression to differentiate into IgE-secreting cells.
体外研究已经证实，Ig 同种型转换通常涉及位于 VDJ 和即将表达的 CH 基因之间的 CH 基因的缺失，并且在此之前该 CH 基因的种系（g）形式会发生转录。细胞因子 IL-4 可诱导 gε 转录水平升高，且总是先于向 IgE 的转换。为了评估在体内是否也存在类似的关系，我们在两个体内系统中检测了 IL-4 mRNA、gε RNA、有功能的（p）ε mRNA 和血清 IgE 水平：一个系统中，注射抗 IgD 抗体可诱导 mIgD⁺ B 细胞转换为 IgE 的表达并分泌该同种型；另一个系统中，注射抗 IgE 抗体可刺激经早期抗 IgD 抗体处理已被诱导表达膜 IgE 的 B 细胞分泌 IgE。在注射抗 IgD 的小鼠中，IL-4 转录水平升高后 24 小时内，gε RNA 增加，1至2天后，pε mRNA 和血清 IgE 水平升高。IL-4 拮抗剂可阻断这些小鼠中 gε 和 pε RNA 以及血清 IgE 的反应，而向未处理的小鼠注射 IL-4 在 24 小时内可刺激 gε RNA 水平大幅增加，1至2天后 pε mRNA 有小幅增加。向用抗 IgD 致敏的小鼠注射抗 IgE 抗体也可刺激 IL-4、gε 和 pε RNA 水平升高；然而，与注射抗 IgD 抗体的小鼠相比，IL-4 和 gε RNA 的升高幅度要小得多，而 pε mRNA 和血清 IgE 的升高幅度要大得多。IL-4 拮抗剂可阻断抗 IgE 抗体诱导的 gε RNA 反应，但不能阻断 pε mRNA 或血清 IgE 反应。因此，在至少两个体内系统中，诱导 gε RNA 需要 IL-4，与体外情况一样，体内 gε RNA 水平升高先于 pε RNA 水平升高，并且诱导已转换为 IgE 表达的 B 细胞分化为分泌 IgE 的细胞既不需要 IL-4 也不需要 gε RNA。
