BACKGROUND: Allergic asthma is a chronic lung disease resulting from inappropriate immune responses to environmental antigens. Early tolerance induction is an attractive approach for primary prevention of asthma. OBJECTIVE: We analysed the mechanisms of perinatal tolerance induction to allergens with particular focus on the role of B cells in preconceptional and early intrauterine immune priming. METHODS: Wild type (WT) and B cell deficient mice received ovalbumin (OVA) intranasally before mating. Their offspring was analysed in a murine model of allergic airway inflammation. RESULTS: While antigen application before conception protected WT progeny from allergy, it aggravated allergic airway inflammation in B cell deficient offspring. B cell transfer restored protection, demonstrating the crucial role of B cells in perinatal tolerance induction. Effective diaplacentar allergen transfer was detectable in pregnant WT mice but not in pregnant B cell KO dams, and antigen concentrations in WT amniotic fluid were higher than in IgG-free amniotic fluid of B cell deficient dams. Application of OVA/IgG immune complexes (IC) during pregnancy boosted OVA uptake by fetal dendritic cells (DCs). Fetal DCs in humans and mice expressed strikingly higher levels of Fcgamma receptors compared to DCs from adults and were highly efficient in taking up OVA-IC. Moreover, murine fetal DCs effectively primed antigen-specific foxp3+ Tregs after in vitro coincubation with OVA/IgG containing amniotic fluid. CONCLUSION: Our data support a decisive role for B cells and immunoglobulins during in utero tolerance priming. These findings improve the understanding of perinatal immunity and may support the development of effective primary prevention strategies for allergy and asthma in the future.
- Happle, C.; Jirmo, A. C.; Meyer-Bahlburg, A.; Habener, A.; Hoymann, H. G.; Hennig, C.; Skuljec, J.; Hansen, G.
Keywords
- Allergy
- Amniotic Fluid
- Asthma
- B cells
- Immune Complexes
- Immunoglobulins
- Perinatal
- Prenatal
- Tolerance
- Tregs
