Mechanisms of IgE homeostasis. Sequestration of IgE by murine type II IgE Fc receptor-bearing B cell hybridomas.
Among all classes of Ig, IgE exhibits the highest rate of fractional catabolism of which the site and mechanisms is not understood. We construct a panel of murine B cell hybridomas to investigate the catabolism of IgE; one of these hybridomas, 17A11, constitutively expresses high levels of type II IgE FcR (Fc epsilon RII, CD23) (Kd:1.77 nM; B max: 1.65 x 10(5], and is capable of clearing receptor-bound IgE. Receptor-mediated endocytosis of IgE ligand ensues after binding monomeric and DNP-BSA:IgE immune complexes, and the binding is inhibited by treating 17A11 with anti-CD23. IgE ligands are sequestered and are not susceptible to acid stripping from the cell surface. The internalized IgE ligands redistributed into acid hydrolase containing high density lysosomal vesicles and were degraded; metabolic inhibitors such as chloroquine and monensin that elevate intracellular pH of 17A11 also prevent entry of IgE ligand into lysosomes. These observations raise the possibility that normal Fc epsilon RII-bearing mature B cells in the circulation and lymphoid tissues may function in sequestration and catabolic turnover of IgE molecules through IgE or IL-4 up-regulated Fc epsilon RII uptake; B cell Fc epsilon RII may perform an important role in determining the short biological half-life of IgE molecules, and contributes to IgE homeostasis.
Chen
S S
SS
Center for Biotechnology, IAN, University of Nebraska-Lincoln 68583-0905.
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D002738:Chloroquine / Q000494:pharmacology; D004705:Endocytosis; D006706:Homeostasis; D006825:Hybridomas / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008985:Monensin / Q000494:pharmacology; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE
D000944:Antigens, Differentiation, B-Lymphocyte; D011961:Receptors, Fc; D017455:Receptors, IgE; D007073:Immunoglobulin E; D002738:Chloroquine; D008985:Monensin