The surface of epithelial cells at mucosal sites is protected from microbial invasion by a fluid which is rich in antibody, usually of the IgA isotype. This IgA antibody is largely produced by local plasma cells lying beneath the secretory epithelium. The precursors of these plasma cells are bone marrow-derived (B) cells which apparently first encounter antigen in the gut-associated lymphoid tissue (GALT) and then follow a unique migration pathway to arrive in the lamina propria at mucosal sites.
The specific aims of this proposal are to examine the ways in which T cells influence the commitment of GALT B cells to IgA and to determine how the IgA-committed B cells migrate to the lamina propria. We have prepared several T cell clones that can be propagated in the presence of Concanavalin A (Con A) or keyhole limpet hemocyanin (KLH) and that help high IgA plaque-forming responses by hapten-primed splenic B cells. We plan to determine whether the T cells actually promote switching to Iga or help proliferation and/or differentiation of IgA bearing B cells. Soluble factors that potentiate the Iga response will be purified and characterized. We also plan to explore the mechanism(s) of migration of normal mesenteric lymph node (MN)-derived B lymphoblasts to the lamina propria of the small intestine. We are especially interested in testing whether they respond to chemotactic signals or bind to endothelial cells in the vasculature of the lamina propria. We hope to be able to prepare monoclonal antibodies against a B lymphoblast surface marker involved in the migration. The long term objectives of the project as a whole are to understand the mucosal immune system well enough to be able to manipulate it. The project is of direct importance to human health. The vast majority of all human pathogens enter the body via mucosal routes: vaccines currently being developed for human use in other laboratories can be most effectively used when we understand how to make them promote immune responses by mucosal lymphoid cells.
|Phillips-Quagliata, J M; Rao, T D; Maghazachi, A A et al. (1992) The IgA receptors of T560, a murine IL-4-secreting, CD5-, IgG2A kappa+, BrMRBC-binding B lymphoma. Ann N Y Acad Sci 651:491-3|
|Rao, T D; Maghazachi, A A; Faria, A M et al. (1992) T560: an (H-2b x H-2a) F1 hybrid, phosphorylcholine (PC)-binding, murine B cell lymphoma that bears receptors for IgA and IgG, presents antigen and secretes IL-4. Int Immunol 4:107-18|
|Phillips-Quagliata, J M; Rao, T D; Maghazachi, A A et al. (1991) Sensitivity of receptors for IgA on T560, a murine B lymphoma, to phorbol myristate acetate and to phosphatidylinositol-specific phospholipase C. Immunol Res 10:432-6|
|Maghazachi, A A; Phillips-Quagliata, J M (1988) Con A-propagated, auto-reactive T cell clones that secrete factors promoting high IgA responses. Int Arch Allergy Appl Immunol 86:147-56|
|Phillips-Quagliata, J M; Maghazachi, A A (1987) T cell clones that help IgA responses. Adv Exp Med Biol 216A:101-17|