Our intent is to define the factors controlling the generation of lasting IgA responses and determine the role of commensal microbes in promoting systemic IgA responses to enteric antigens and pathogens. The central hypothesis underpinning this work is that Segmented Filamentous Bacteria (SFB) promote systemic IgA responses by priming gut-resident T and B cells, thus augmenting the generation of mucosal IgA+-secreting cells that subsequently colonize niches for long-lived plasma cells in the bone marrow. Additional experiments will define the life span of IgA-secreting plasma cells in the gut and the bone marrow, at steady state and in response to an enteric pathogen. Specifically we will: 1) Define the impact of SFB colonization on the bone marrow plasma cell pool, 2) Define the impact of SFB colonization on systemic IgA responses to enteric microbes, 3) Define decay kinetics for IgA+ PCs in the LP and the BM.
The factors underlying the generation of long-lived IgA antibody responses to enteric antigens and pathogens are poorly understood. These studies will establish the role of commensal microbes in the gut mucosa on systemic IgA responses. These studies have direct implications for the design of oral vaccines to a wide variety of enteric pathogens.