Lifelong Memory Responses Perpetuate Humoral Th2 Immunity and Anaphylaxis in Food Allergy

Publication date: Available online 16 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Rodrigo Jiménez-Saiz, Derek K. Chu, Talveer S. Mandur, Tina D. Walker, Melissa E. Gordon, Roopali Chaudhary, Joshua Koenig, Sarah Saliba, Heather J. Galipeau, Adam Utley, Irah L. King, Kelvin Lee, Rachel Ettinger, Susan Waserman, Roland Kolbeck, Manel Jordana
BackgroundA number of food allergies (e.g. fish, shellfish, nuts) are lifelong, without any disease-transforming therapies and unclear in their underlying immunology. Clinical manifestations of food allergy are largely mediated by IgE. Although persistent IgE titres have conventionally been attributed to long-lived IgE⁺ plasma cells (PCs), this has not been directly and comprehensively tested.ObjectiveTo evaluate mechanisms underlying persistent IgE and allergic responses to food allergens.MethodsWe used a model of peanut allergy and anaphylaxis, various knockout mice, adoptive transfer experiments and in vitro assays, to identify mechanisms underlying persistent IgE humoral immunity over almost the entire life-span of the mouse (18-20 months).ResultsContrary to conventional paradigms, our data show that clinically relevant lifelong IgE titres are not sustained by long-lived IgE⁺ PCs. Instead, lifelong reactivity is conferred by allergen-specific long-lived memory B cells that replenish the IgE⁺ PC compartment. B cell re-activation requires allergen re-exposure and IL-4 production by CD4 T cells. We define the half-lives of antigen-specific: germinal centers (23.3 days); IgE⁺ and IgG1⁺ PCs (60 days and 234.4 days respectively) and clinically-relevant cell-bound IgE (67.3 days).ConclusionsThese findings can explain lifelong food allergies observed in humans as the consequence of allergen exposures that recurrently activate memory B cells and identify these as a therapeutic target with disease-transforming potential.

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Capsule Summary: R. Jimenez-Saiz and D.K. Chu et al. examine lifelong IgE responses in food allergy and identify that allergen-specific long-lived memory B-cells and IL-4 producing CD4 T cells are critical to this process by re-generating reservoirs of IgE-secreting plasma cells.


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