Memory Generation and Re-Activation in Food Allergy

Abstract

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, although how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation, specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

Keywords:

• food allergy
• IgE
• memory responses
• anaphylaxis
• B cells
• T cells

Abbreviations

PCs, plasma cells; MBCs, memory B cells; PBMCs, peripheral blood mononuclear cells; CSR, class-switch recombination; BCRs, B-cell receptors; OVA, ovalbumin; SLOs, secondary lymphoid organs; PN, peanut; AIT, allergen immunotherapy; sc-RNAseq, single-cell RNA sequencing; DCs, dendritic cells; TCR, T-cell receptor; Treg, T regulatory; Tfh, T follicular helper; Tfr, T follicular regulatory; Trm, tissue-resident memory.

Acknowledgments

We acknowledge Adam Wade-Vallance and Claud Spadafora for critically reviewing the manuscript and for illustrating the figures, respectively. RJS acknowledges the support received by the Severo Ochoa Program (AEI/SEV-2017-0712), FSE/FEDER through the Instituto de Salud Carlos III (ISCIII; CP20/00043), The Nutricia Research Foundation (NRF-2021-13) and New Frontiers in Research Fund (NFRFE-2019-00083). Research in MJ’s laboratory is supported by funds from Food Allergy Canada, Walter and Maria Schroeder Foundation, Michael Zych Family, the Canadian Asthma, Allergy, and Immunology Foundation (CAAIF) and ALK-Abello.

Disclosure

JFEK, KB, AP, EG and MJ report grants from Food Allergy Canada,the Walter and Maria Schroeder Foundation, the Michael Zych Family, the Canadian Asthma Allergy and Immunology Foundation, and ALK-Abello, outside the submitted work. The authors report no other potential conflicts of interest in relation to this work.