UC Riverside

Our mucosal immune system responds to pathogens and commensals on mucosal surfaces by forming a tight barrier and producing immunoglobulin A (IgA). IgA production depends on the uptake of gut lumen particulates by specialized epithelial cells called microfold (M) cells and the subsequent B cell activation in the mucosal lymphoid tissue. B-1 and B-2 B cells are two main B cell subset responsible in generating immune response at the mucosal site. Although B-1B cells has been shown to contribute to T- cell independent immune response while B-2 B cell use mainly T-cell dependent pathway, studies have suggested that both of these subset contribute IgA production in the gut almost equally. However, contrary to B-2 B cells, the location where B-1 B cell activated by mucosal antigen has remained unclear. Additionally, tumor necrosis factor (TNF) receptor/ligand superfamily signaling has been shown to play a role in mucosal lymphoid tissue organogenesis and M cell uptake function such that lymphotoxin (LT)-α-/-, LT-β-/-, LT-βR-/- or CD137-/- mice have no Peyer's patches or a very low IgA titer. In-vitro treatment with TNFα is also known to decrease epithelial barrier function. Henceforth, this study will highlight the potential use of recombinant IgA in clearing the replicating dengue virus in the gut, the B-1 B cell contribution in mucosal immune response, and the role of a TNF superfamily receptor, CD137, in the intestinal epithelial cells. Peritoneal B-1 B cells generate antigen specific IgG and IgM when the mice immunized intraperitoneally or subcutaneously, but not intranasally, using polymeric vaccine. The last chapter of this study further characterizes the role of CD137 in intestinal epithelial cells by utilizing an in-vitro overexpression system, which could further reveal the biological relevance of TNFα in chronic intestinal inflammation. Our seminal findings describe the role of CD137 in increasing tight junction resistance and its association with actin filament termini. In sum, this study addresses how a receptor, CD137, known for its co-stimulatory function in immune cells activation can mediate the physical barrier created by intestinal epithelial cells, the humoral response of B-1 B cells in mucosal immunity and the use of recombinant IgA as therapy.