Genesis of host IgE competence: perinatal IgE tolerance induced by IgE processed and presented by IgE Fc receptor (CD23)-bearing B cells.
A murine model for studying life-long IgE tolerance was previously developed in this laboratory by perinatal IgE injection into neonates. Herein, we demonstrated that normal and immortal CD23+ B cell lines presented processed IgE via CD23-mediated endocytic pathway and triggered perinatal IgE tolerance. The observations were as followed: (a) CD23 on normal B cells or B cell hybridomas mediated IgE-dependent perinatal IgE tolerance and total IgE deficiency; and lack of either antigen-specific IgE or total IgE did not correlate with elevated levels of autologous anti-IgE in individual mice; (b) IgE tolerance-inducing capacity of CD23+ B cell hybridomas was augmented by treatment with antigen-IgE complexes or interleukin 4, and significantly inhibited by anti-CD23 prior to IgE pulsing; (c) antigen-IgE complexes were endocytosed and degraded in acid hydrolases-containing vesicles; and IgE tolerance was abrogated by treating IgE-pulsed 17A11 at 4 degrees C or 20 degrees C followed immediately by fixation, and by treating IgE-pulsed 17A11 with metabolic inhibitors that elevated intracellular pH of the endocytic vesicles. In conclusion, this study suggested that one pivotal step of genetic control of IgE responses may be exercised at the early developmental stage of T cells of the IgE lineage, and that CD23 may facilitate capture of endogenously secreted IgE, and mediate endocytic processing and presentation of self IgE epitope(s), and thus contribute to the genesis of host IgE competence.
Chen
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Department of Veterinary Science, School of Medicine, University of Nebraska, Lincoln 68583-0905.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D004705:Endocytosis / Q000187:drug effects; D006825:Hybridomas; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008985:Monensin / Q000494:pharmacology; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE
D000944:Antigens, Differentiation, B-Lymphocyte; D011961:Receptors, Fc; D017455:Receptors, IgE; D007073:Immunoglobulin E; D008985:Monensin