IgE Generation and Mast Cell Effector Function in Mice Deficient in IL-4 and IL-13

• Published in: The Journal of immunology (1950) Vol. 174; no. 12; pp. 7716 - 7724
• Main Authors: Fish, Susan C, Donaldson, Debra D, Goldman, Samuel J, Williams, Cara M. M, Kasaian, Marion T
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-06-2005
• Subjects: Animals; Binding Sites, Antibody - genetics; Cell Count; Cell Degranulation - genetics; Cell Degranulation - immunology; Cell Separation; Dose-Response Relationship, Immunologic; Immunization, Secondary; Immunoglobulin E - biosynthesis; Immunoglobulin E - blood; Immunoglobulin E - deficiency; Immunoglobulin E - physiology; Interleukin-13 - deficiency; Interleukin-13 - genetics; Interleukin-13 - metabolism; Interleukin-13 - physiology; Interleukin-4 - deficiency; Interleukin-4 - genetics; Interleukin-4 - metabolism; Interleukin-4 - physiology; Mast Cells - immunology; Mast Cells - metabolism; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin - administration & dosage; Ovalbumin - immunology; Passive Cutaneous Anaphylaxis; Peritoneal Cavity - cytology; Protein Binding - genetics; Protein Binding - immunology; Protein Subunits - deficiency; Protein Subunits - genetics; Receptors, Interleukin-4 - deficiency; Receptors, Interleukin-4 - genetics; Up-Regulation - genetics; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.12.7716

IL-4 and IL-13 are potent cytokines that drive production of IgE, which is critical to the development of atopic disease. In this study, we directly compared IgE generation and IgE-dependent mast cell effector function in mouse strains lacking IL-4, IL-13, IL-4 + IL-13, or their common receptor component, IL-4Ralpha. Although serum IgE was undetectable under resting conditions in most animals deficient in one or both cytokines, peritoneal mast cells from mice lacking IL-4 or IL-13 had only partial reductions in surface IgE level. In contrast, peritoneal mast cells from IL-4/13(-/-) and IL-4Ralpha(-/-) animals were severely deficient in surface IgE, and showed no detectable degranulation following treatment with anti-IgE in vitro. Surprisingly, however, intradermal challenge with high concentrations of anti-IgE Ab induced an ear-swelling response in these strains, implying some capacity for IgE-mediated effector function in tissue mast cells. Furthermore, upon specific immunization with OVA, both IL-4/IL-13(-/-) and IL-4Ralpha(-/-) mice produced detectable levels of serum IgE and Ag-specific IgG1, and generated strong ear-swelling responses to intradermal administration of anti-IgE. These findings suggest that a mechanism for IgE production exists in vivo that is independent of IL-4 or IL-13.