Superinduction of the murine B cell Fc epsilon RII by T helper cell clones. Role of IL-4.

Th cell clones are known to induce an IL-4 dependent polyclonal IgE synthesis. Because IL-4 can induce the expression of the low affinity FcR for IgE (Fc epsilon RII) the ability of Th cell clones to induce Fc epsilon RII on purified splenic B cells was analyzed. It was found that a TH2 clone could cause a 50- to 100-fold superinduction of Fc epsilon RII after 2 days in culture; after 3 days, the Fc epsilon RII levels had almost returned to base line. The superinduction was inhibited by an anti-IL-4 antibody, 11B11, indicating its dependence on IL-4. A TH1 clone could cause a modest (four fold) induction of Fc epsilon RII, and this induction was not influenced by 11B11. A similar Fc epsilon RII induction was seen when using the supernatant from activated TH1 cells. The component(s) causing this relatively low level Fc epsilon RII induction is not known; a variety of known lymphokines were tested, and only IL-4 demonstrated any capacity for Fc epsilon RII induction on LPS-activated B cells. Addition of rIL-4 at concentrations of 400 U/ml or greater to the TH1 culture was sufficient to cause a Fc epsilon RII superinduction similar to that seen with the TH2 clone, while 40 U/ml was not. In order to determine a potential role for the Fc epsilon RII or its soluble fragment on the IgE synthesis mediated by TH2, a monoclonal anti-Fc epsilon RII, B3B4, was added to the culture. The addition of B3B4 did not have an influence on IgE levels in this system.

Superinduction of low affinity IgE receptors on murine B lymphocytes by lipopolysaccharide and IL-4.

Recent work in both the human and murine systems has demonstrated that IL-4 is capable of specifically inducing the synthesis of the low affinity receptor for IgE (Fc epsilon RII). In addition, in conjunction with LPS, IL-4 will induce IgG1 and IgE synthesis. To analyze the correlation between Fc epsilon RII induction and IgE secretion, Fc epsilon RII and IgE levels were measured by RIA on murine splenic B cells stimulated with LPS and IL-4 over 7 days of culture. Treatment with LPS and IL-4 gave a 20- to 50-fold (day 3) "superinduction" of Fc epsilon RII levels compared with a 3- to 5-fold induction with IL-4 alone; removal of IL-4 resulted in a rapid decline in Fc epsilon RII levels. The cells expressing high Fc epsilon RII levels were determined to be blasts. Superinduction of Fc epsilon RII occurs at 10 U/ml IL-4 and remains relatively constant in the range of 10 to 1000 U/ml. In contrast, with increasing IL-4, IgE levels increase, reaching microgram levels at day 7 with 300 U/ml IL-4. Triggering the cells with anti-Ig, as expected, gave no Ig secretion, and in addition, Fc epsilon RII superinduction by IL-4 and anti-Ig was not seen. PMA is known to block Ig secretion induced by LPS. Concentrations of PMA that totally abrogated IgE secretion had no effect on Fc epsilon RII superinduction, indicating that the latter phenomena can be separated from IL-4-induced Ig secretion. Superinduction also results in higher levels of Fc epsilon RII fragment release into the media. Thus, attempts were made to influence IgE secretion by adding additional purified Fc epsilon RII fragment to the culture. The purified fragment did not have a significant influence on IgE levels in this system.