IgE generation and mast cell effector function in mice deficient in IL-4 and IL-13.
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.
Fish
Susan C
SC
Wyeth Research, Cambridge, MA 02140, USA.
Donaldson
Debra D
DD
Goldman
Samuel J
SJ
Williams
Cara M M
CM
Kasaian
Marion T
MT
D000818:Animals; D001666:Binding Sites, Antibody / Q000235:genetics; D002452:Cell Count; D015550:Cell Degranulation / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D004306:Dose-Response Relationship, Immunologic; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood / Q000172:deficiency / Q000502:physiology; D018793:Interleukin-13 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015847:Interleukin-4 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis; D010529:Peritoneal Cavity / Q000166:cytology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000172:deficiency / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D018793:Interleukin-13; D021122:Protein Subunits; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin