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 1

The majority of aeNP+ cells are B cells.

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The majority of aeNP+ cells are B cells. On days 0 and 7, BALB/cJ mice w...
On days 0 and 7, BALB/cJ mice were sensitized i.p. with either OVA and alum, peanut extract (PE) and alum, or PBS for healthy controls. All mice received treatment with 2.5 mg of i.v. Cy5.5-conjugated OVA NPs on days 14 and 21. Mesenteric lymph nodes (mLNs), Peyer’s patches (PPs), small intestine lamina propria (SILP), and splenocytes were isolated and analyzed via flow cytometry on days 15 and 22 to identify OVA NP–associated cells. (A) Biodistribution of OVA NPs with lymphocytes and myeloid cells across tissues in OVA-alum–sensitized mice. (B) In the SILP, the percentage of NP+ B cells of all NP+ cells across different sensitizations. (C) In the SILP, the proportion of NP+ B cells of all B cells across different sensitizations. (D) In the SILP, the percentage of B cells of all live cells across sensitizations. Data shown as mean ± SD; statistically significant differences were identified using 2 way-ANOVA with a post hoc Šidák’s test; P values are shown above significance brackets and sample size at the bottom of each bar (n = 4–5). *P < 0.05, **P < 0.01.