Germline and Productive C-Epsilon-Gene Expression during in-Vivo Ige Responses
(EN)
Thyphronitis, G.
(EN)
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών
(EL)
Thyphronitis, G.
(EN)
In vitro studies have established that Ig isotype switching typically involves deletion of C(H) genes that are located between VDJ and the C(H) gene that will be expressed, and is preceded by transcription of a germline (g) form of that C(H) gene. Increases in gepsilon 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, gepsilon 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 gepsilon RNA, and, one to two days later, by increased pepsilon mRNA and serum IgE levels. IL-4 antagonists blocked the gepsilon and pepsilon 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 gepsilon RNA levels, followed 1-2 days later by a small increase in pepsilon mRNA. Injection of anti-IgD-primed mice with anti-IgE antibody also stimulated increases in IL-4, gepsilon, and pepsilon RNA levels; however, the increases in IL-4 and gepsilon RNA were considerably smaller, and the increases in pepsilon mRNA and serum IgE considerably larger, than those observed in anti-IgD antibody-injected mice. IL-4 antagonists blocked the anti-IgE antibody-induced gepsilon RNA response, but not the pepsilon mRNA or serum IgE responses. Thus, IL-4 is required for the induction of gepsilon RNA in at least two in vivo systems, increased gepsilon RNA levels precede increases in pepsilon RNA levels in vivo as in vitro, and neither IL-4 nor gepsilon RNA is required to induce B cells that have already switched to IgE expression to differentiate into IgE-secreting cells.
(EN)
