B cell memory in human food allergy

Summary High affinity IgE antibodies are essential mediators of food allergy, a main cause of life-threatening anaphylaxis. Most food allergies develop in childhood and affect children disproportionally. A long-standing question in the allergy field is why allergies to some foods spontaneously cure, while others persist. A key to understanding the evolution of food allergy may reside in the mechanisms that maintain the B cell memory of high affinity IgE responses. Experimental studies from our group demonstrated that IgE cells exist mostly as plasma cells and not IgE memory cells, and that high affinity pathogenic IgE antibodies derive from the sequential switching of affinity matured IgG1 memory B cells. While the origin of human high affinity IgE is not definitely proved, an increasing body of work supports a precursor role of IgG memory cells in the generation of human pathogenic IgE plasma cells. We hypothesize that the existence of high affinity food-specific IgG cells and their ability to undergo class switching to IgE are critical for allergy persistence. Preliminary studies from our group suggest that atopic individuals harbor B lymphocytes with a distinct profile that increases their response to activation and differentiation into IgE plasma cells. We postulate that the atopic immune environment marks allergen-specific IgG memory cells with a ‘pro-allergic’ signature, and that the presence of these pro-allergic memory cells is necessary for the development and persistence of food allergy. We propose to investigate the existence of pro- allergic memory B lymphocytes in food allergic children, in children that outgrew their food allergy, in tolerant never-allergic children, and in children with non-allergic inflammatory disease. We will determine if memory B cells that recognize food allergens have a specific phenotype that distinguish them from memory B cells that recognize virus and vaccines antigens in allergic and non-allergic children. We expect that the findings from this study will provide tools to predict food-allergy risk and persistence, and help to design new therapies for allergic diseases.