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
Figure 6
OVA NP treatment induces distinct IL-10+ regulatory B cell phenotype and crosstalk.
