B cells control maternofetal priming of allergy and tolerance in a murine model of allergic airway inflammation

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:141

Article

Happle, Christine^1,2,3  Jirmo, Adan Chari^1,2,3  Meyer-Bahlburg, Almut^1,2,3,4  Habener, Anika^1,2,3  Hoymann, Heinz Gerd⁵  Hennig, Christian^1,2,3  Skuljec, Jelena¹  Hansen, Gesine^1,2,3 

[1] Hannover Med Sch, Dept Pediat Pneumol Allergol & Neonatol, Carl Neuberg Str 1, D-30625 Hannover, Germany

[2] Biomed Res Endstage & Obstruct Lung Dis BREATH, Hannover, Germany

[3] German Ctr Lung Res DZL, Hannover, Germany

[4] Univ Med Greifswald, Dept Pediat, Greifswald, Germany

[5] Fraunhofer Inst Toxicol & Expt Med Hannover, Working Grp Airway Pharmacol, Hannover, Germany

关键词: Allergy;    asthma;    tolerance;    perinatal;    prenatal;    B cells;    regulatory T cells;    immunoglobulins;    immune complexes;    tolerance;    amniotic fluid;   

DOI  :  10.1016/j.jaci.2017.03.051

来源: Elsevier

【 摘 要 】

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 analyzed the mechanisms of perinatal tolerance induction to allergens, with particular focus on the role of B cells in preconception and early intrauterine immune priming. Methods: Wild-type (WT) and B cell-deficient mice received ovalbumin (OVA) intranasally before mating. Their offspring were analyzed in a murine model of allergic airway inflammation. Results: Although 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 knockout dams, and antigen concentrations in WT amniotic fluid (AF) were higher than in IgG-free AF of B cell-deficient dams. Application of OVA/IgG immune complexes during pregnancy boosted OVA uptake by fetal dendritic cells (DCs). Fetal DCs in human subjects and mice expressed strikingly higher levels of Fc gamma receptors compared with DCs from adults and were highly efficient in taking up OVA/IgG immune complexes. Moreover, murine fetal DCs effectively primed antigen-specific forkhead box P3(+) regulatory T cells after in vitro coincubation with OVA/IgG-containing AF. 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 might support the development of effective primary prevention strategies for allergy and asthma in the future.

【 授权许可】

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