The murine lymphocyte receptor for IgE. IV. The mechanism of ligand-specific receptor upregulation on B cells.
Rodent B cells respond to culture with IgE by increasing their IgE-specific Fc receptors (Fc epsilon R). The mechanism of this upregulation was characterized on Fc epsilon R+ murine B cell hybridoma lines. Measurements of [35S]methionine incorporated into the Fc epsilon R over time indicated that IgE did not appreciably increase the rate of Fc epsilon R synthesis. In contrast analysis of Fc epsilon R decay from surface radioiodinated B hybridoma cells demonstrated that IgE acted to slow the rate of Fc epsilon R degradation. Very little endocytosis of monomeric IgE was seen; this, combined with the observation that lysomotropic agents failed to inhibit Fc epsilon R degradation suggested that decay occurs at the cell surface. A soluble receptor immunoassay was developed, using monoclonal anti-Fc epsilon R, and this assay demonstrated that cell-bound IgE inhibited the release into the culture media of soluble immunoreactive Fc epsilon R. Examination of the soluble Fc epsilon R by SDS-PAGE after isolation with monoclonal anti-Fc epsilon R demonstrated that it was 10,000 m.w. smaller than the cell-associated Fc epsilon R. IgE affinity columns failed to bind the Fc epsilon R fragment, indicating that the ligand binding activity was largely lost. Thus this study demonstrated that IgE-dependent Fc epsilon R induction on B cells occurs because IgE upon binding to the B cell surface, inhibits the proteolytic cleavage and release of the Fc epsilon R into the surrounding medium, and it is this inhibition of degradation that causes the higher Fc epsilon R levels.
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D004705:Endocytosis; D007073:Immunoglobulin E / Q000502:physiology*; D007700:Kinetics; D008024:Ligands; D008247:Lysosomes / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008970:Molecular Weight; D011961:Receptors, Fc / Q000096:biosynthesis / Q000502:physiology*; D017455:Receptors, IgE; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D012995:Solubility
D008024:Ligands; D008565:Membrane Proteins; D011961:Receptors, Fc; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D007073:Immunoglobulin E