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 shown to induce regulatory B cell (Bregs) 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+ dendritic cells (DCs) and CCR9+ gut-homing regulatory T cells, 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 have been 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.