Mucosal antibodies in the regulation of tolerance and allergy to foods

Abstract

The intestinal mucosa is densely packed with antibody-secreting B cells, the majority of which produce IgA. Mucosal antibodies have traditionally been thought of as neutralizing antibodies that exclude antigens, but they also function in antigen sampling, allowing for selective transcytosis of antigens from the intestinal lumen. IgE-mediated antigen uptake can facilitate the development of allergic reactions to foods, but emerging evidence indicates that IgG-mediated antigen uptake may also play an important role in the development of immune tolerance to foods, particularly in the neonate. This review will focus on the role of intestinal immunoglobulins in the development of clinical tolerance and allergy to food antigens.

IgA deficiency: a risk factor for food allergy-related atopic dermatitis in infants and young children

“…Therefore, defects in mounting a sufficient response against penetrating pathogens and failure to support the commensal organisms in the gastrointestinal tract in immunodeficient children predispose them to the breakdown of oral tolerance and to the subsequent development of food allergy, inflammatory bowel disease and infections [11]. Furthermore, the gastrointestinal tract is the largest immunological organ in the human body, rich in antibody-secreting plasma cells and an essential source of mucosal and circulating IgA and, to a lesser extent, also IgM and IgG isotypes playing a prominent role in mucosal compartmentalization of food antigens and protecting against allergic sensitization to foods [12][13][14]. Systemic sensitization to foods may thus reflect a lack of appropriate, antibody-dependent compartmentalization of food antigens.…”

Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways

“…This process is regulated by T follicular helper (T FH ) and T follicular regulatory cells (T FR ) (Kawamoto et al, 2014). IgA deficiency has been linked to exacerbated colitis (Cao et al, 2012) and systemic inflammation (Kawamoto et al, 2012) and is also likely to be associated with allergic diseases (Berin, 2012;Kukkonen et al, 2010).…”

Re-thinking the functions of IgA+plasma cells

“…IgA entraps Ag and affects microbial virulence within cells and the mucus and prevents binding to cells and dissemination. 12,[76][77][78][79] IgA has been shown to bind to several receptors including FcaRI (CD89), transferrin receptor (CD71), a receptor for the secretory component, Galectin-1 and a microfold-cell IgA receptor, all of which have distinct expression patterns on myeloid, lymphoid or non-haematopoietic cells. 6 Interaction of the Fc region of IgA with its receptors instructs and regulates intestinal innate and adaptive immunity through regulation of cellular functions upon ligation of IgA receptors.…”