Intestinal immune responses involve detection of pathogens in gut-associated secondary lymphoid tissues and migration of effector cells, via the lymph and blood, to other sites, including the intestinal lamina propria, where the threat to the host can be neutralized. It is widely hypothesized that the expression of specific intestinal homing receptors target effector and memory cell migration to the gut wall, but the regulation of HR expression during physiologic immune response has not been studied. Murine rotavirus (RV), which exclusively infects and proliferates in intestinal epithelial cells provides a model of an intestine-specific pathogen for which antigen specific B cells can be detected and analyzed. Here I propose to determine the temporal sequence in which rotavirus specific B cells appear in intestinal Peyer's patches (PP), mesenteric lymph nodes (MLN), spleen, bone marrow (BM), and intestinal lamina propria (LP); to define the B cells' developmental stage through analyses of their cell surface phenotype and/or expression of cytoplasmic or secreted Ig, and the isotype of antibody produced; to determine their expression of specific homing receptors involved in trafficking to intestinal sites and to characterize their responses to chemotactic cytokines. These studies should define critical developmental transitions in homing properties and provide a framework for considering the alterations in B cell phenotype (and associated shifts in the localization of antigen-specific populations) during development of the humoral immune response. They also constitute the first direct assessment of the regulation of chemokine/chemoattractant responses on lymphocytes participating in a physiologic immune response. Definition of unique chemoattractant responses characteristic of intestinal vs. peripheral immunization, or of defined stages in the intestinal B cell response to antigen, could lead to novel approaches to the therapeutic modulation of tissue-specific immune responses in vivo.
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