Regulatory B cells contribute to allergen-encapsulating nanoparticle immunotherapy efficacy for food allergy
Laila M. Rad, Michael N. Saunders, Laura A. Williams, Katarzyna W. Janczak, Chris Dorsett, Kate V. Griffin, Elizabeth J. Bealer, Jeffrey A. Ma, Sayre A. Tillery, Jyotirmoy Roy, Stephen D. Miller, Jessica J. O’Konek, Lonnie D. Shea
Laila M. Rad, Michael N. Saunders, Laura A. Williams, Katarzyna W. Janczak, Chris Dorsett, Kate V. Griffin, Elizabeth J. Bealer, Jeffrey A. Ma, Sayre A. Tillery, Jyotirmoy Roy, Stephen D. Miller, Jessica J. O’Konek, Lonnie D. Shea
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Research Article Cell biology Immunology

Regulatory B cells contribute to allergen-encapsulating nanoparticle immunotherapy efficacy for food allergy

Abstract

B cells contribute to the pathogenesis of food allergies as they induce allergen-specific antibody production. Clinically used allergen-specific immunotherapies have been shown to induce regulatory B cell subsets as well as target and reduce allergy-driving B cell functions. This report aims to elucidate the contribution of regulatory B cells to an allergen-encapsulating nanoparticle (aeNP) immunotherapy in a murine model of food allergy. In this model, B cells directly associated with aeNPs. CD20+ B cell depletion after aeNP treatment increased the number of mice with severe allergic reactions during oral food challenges and reduced the expansion of regulatory immune cells including CD103+ DCs and CCR9+ gut-homing Tregs, indicating that B cells are a component of aeNP immunomodulation. B cell communication in the gastrointestinal tract of aeNP-treated mice identified CD23 signaling as a potential inducer of regulatory CD103+ DC functions and disrupter of allergy-driving B cell–T cell communication. These tolerogenic signaling patterns were also identified in IL-10+ B cells, which are known to impart regulatory immune effects in both murine and human disease. Ultimately, B cells are a component of the complex immunomodulation leading to aeNP efficacy at reducing allergic reactivity.

Authors

Laila M. Rad, Michael N. Saunders, Laura A. Williams, Katarzyna W. Janczak, Chris Dorsett, Kate V. Griffin, Elizabeth J. Bealer, Jeffrey A. Ma, Sayre A. Tillery, Jyotirmoy Roy, Stephen D. Miller, Jessica J. O’Konek, Lonnie D. Shea

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Figure 5

Single-cell RNA-Seq of the SILP identifies changes in B cell communication after aeNP treatment.

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Single-cell RNA-Seq of the SILP identifies changes in B cell communicati...
Mice sensitized with OVA-alum on days 0 and 14 were treated with OVA NPs on days 28 and 42, and SILP were harvested for single-cell RNA-Seq after OFC 7 on day 60. (A) Cell types from all samples are shown in the UMAP. (B) The proportion of B cell lineage cell types of all cell types by treatment. (C) CellChat was used to do receptor-ligand cell communication analysis. Signaling networks at OFC 7 of allergic and OVA NP–treated SILP ranked based on the number of interactions for B cells as source and target cells. Signaling pathway names labeled in red or blue in PBS- or OVA NP–treated mice, respectively, are significantly different by paired Wilcoxon’s test (P < 0.05). Circle plot (D) or chord diagrams (E and F) show arrows going from source cells to target cells. Receptor, ligand genes, or cell type names are placed on the outside circumference. (D) IL-4 signaling at OFC 7 for both PBS- and OVA NP–treated SILP. (E) Upregulated CD23 signaling in SILP of OVA NP–treated mice from PBS controls at OFC 7. (F) Upregulated MHC-II signaling at OFC 7 in SILP of OVA NP–treated and PBS-treated mice. Data subsets: only Th2 T cells, Tregs, and naive CD4+ T cells were target cells and only DCs, CD103+ DCs, B cells, and IgG1+ B cells were sender cells. Illustration of immune cell communication was created in BioRender.