B Cell Responsiveness to IL-10 and Regulation of IgE and IgG4 Production
Following oral immunotherapy, food-specific IgE levels in the serum decrease, while food-specific IgG4 levels increase. Food-specific IgG4 has been associated with natural or acquired tolerance to peanut and cow’s milk. Increases in food-specific IgG4 have also been observed with introduction and regular consumption of peanut and egg. These findings suggest that consuming tolerated food promotes food-specific IgG4 production and that food-specific IgG4 may be indicative of tolerance. The cytokine Il-10 can downregulate B cell class switch to and production of IgE, while also augmenting class switch to and production of IgG4; however, the ability of B cells to bind and respond to IL-10 may be altered in children with food allergy. Through investigation of these alterations, we will provide new data concerning the importance of B cells in the context of food allergy, potentially uncovering new therapeutic targets and/or biomarkers for tolerance.
The Role of Regulatory B Cells in Food Allergy, Sensitization and Tolerance
IL-10-producing T and B cells are increased following allergen immunotherapy but have not been well studied in the context of food allergy and oral immunotherapy. Recent studies in infants and children with peanut allergies show no difference in the frequency or stability of peripheral, peanut-specific regulatory T cells, suggesting that other regulatory cells, such as regulatory B cells (B regs), may be important. B regs are capable of producing IL-10 and IgG4 and have been shown to be decreased in the periphery of individuals with food allergies compared to nonallergic controls. Indeed, a previous study demonstrated a lower frequency of peripheral IL-10+ B cells in adults with food allergies compared to nonallergic controls. Our examination of differences in the frequency and function of B regs between children with food allergies versus children without food allergies will determine the role of these cells in the development of food allergy versus tolerance.
Regulation of B Cells by the Herbal Compound Berberine
Given the importance of IgE in allergic disease, researchers are examining ways to inhibit IgE production. Chinese herbal medicines have been used in Asia for centuries to treat many diseases, including allergy. They are also used in Western countries as alternative or complementary medicine. Berberine is a compound found in several herbal medicines. Our collaborator, Dr. Xiu-Min Li at New York Medical College, has discovered that berberine decreases B cell production of IgE, making berberine a good candidate for food allergy treatment; however, we do not know much about how berberine works at the cellular level. We are working to determine the mechanisms underlying berberine’s effects on the production of IgE and other antibody isotypes as well as its effects on other aspects of B cell biology.