Nutritional regulation of genes associated with avian B cell receptors involved in innate and adaptive immunity

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Reducing the use of antimicrobials in the rearing of poultry can be achieved by enhancing the natural immunity of chickens, thus minimizing disease and pathogen shedding. Intervention of the immune system of the chick in ovo has a dramatic effect on the immunity of the bird post-hatch, increasing its ability to resist a disease challenge. However, it is not only the chick's immune system that must be strengthened but also that of the adult bird. The nutritional status of the laying hen directly influences the nutrient composition of the egg and, in turn, the development and nutritional status of the embryo and hatchling. This has implications for epigenetic regulation of gene expression allowing dividing cells to memorize, or imprint, signalling events that occurred earlier in their development. Folate plays a critical role in nucleic acid and protein synthesis; a deficiency of folate significantly alters the immune response. My hypothesis is that the inclusion of folate in breeder hens' diet will enhance B cell development in the embryo by influencing B cell precursor development through BCR and TCR gene methylation status. In this research program, correlation between early host innate and adaptive immune system development and maturation will be used to explain epigenetic regulation at the antigen receptors (BCR and TLR) and cytokine production as the cells mature. This program will furthermore integrate epigenetic characterization, B cell development, and immunity evaluation with oral nutrition intervention using folate-producing probiotics as epigenetic modifiers. The main objectives of this research program are to: (1) Study epigenetic changes associated with BCR intracellular signalling protein Igß, MHC II, and TLR-2 and TLR-4 genes in B cell precursors, and identify genes under methylation regulation; (2) Determine whether inclusion of methyl donor is correlated with DNA methylation in V(D)J recombination and in the predicted promoter region of TLR-2 and TLR4 genes; (3) Determine whether epigenetic programming via DNA methylation regulates gene expression. The outcome of this research will not only have important practical application for the poultry industry, but will also yield a better understanding of how chromatin remodelling mediated by DNA methylation and demethylation plays a major role in regulating V(D)J regions recombination and germ line transcription through the BCR and TCR. The information will improve our understanding of B cell development and maturation in chicken embryos, and will develop models integrating nutritional intervention and epigenetic immune outcome. Determining the effect of probiotics in boosting the immune response is critical to the future of the Canadian Poultry Industry (nutrition and animal health) as it will help determine which breeding stage (laying hens, broilers, etc.) may benefit the most from nutritional intervention strategies**