The IgE Antibody System Is Coordinately Regulated by FcR Epsilon-Positive Lymphoid Cells and IgE-Selective Soluble Factors

Abstract

Recent studies in mice have demonstrated that exposure of lymphocytes to appropriate levels of IgE initiates a cascade of cellular and molecular interactions which function as a network to control IgE synthesis. A key manifestation of these events is the expression of Fc receptors for IgE (FcRε) on both B and T lymphocytes, and the fact that such expression of FcRε can be selectively modulated by the isotype-specific regulatory mediators, suppressive factor of allergy (SFA) and enhancing factor of allergy (EFA). In humans, we have previously shown that the in vitro induction by pokeweed mitogen (PWM) of IgE biosynthesis by peripheral blood lymphocytes (PBL) can also be selectively suppressed by SFA. Herein we show that PWM also induces expression of FcRε+ and FcRγ+ cells among human PBL by day 2 or 3 in culture, and this early development of FcRε+ lymphocytes appears to be a coordinate event with the ultimate de novo synthesis of IgE in this system. Moreover, as previously documented for IgE synthesis, the presence of SFA causes a 50% reduction of FcRε+ cells induced by PWM. This inhibition is selective, since FcR+ cells for IgG are not affected by exposure to human SFA derived from a recently constructed human T cell hybridoma line which constitutively secretes large quantities of biologically active human SFA. These findings further support the regulatory role that FcRε+ lymphocytes must play in the development of IgE responses by human cells in vitro, and suggest a mechanism by which SFA can selectively inhibit IgE synthesis in PWM-stimulated cultures of human PBL.