Peyer's patches and other mucosal lymphoid follicles may play several roles in the generation of a secretory immune response manifest at a particular near or distant site: (1) 'antigen-sampling' accomplished by passage of intact macromolecules through specimized dome epithelial cells; (2) clonal expansion of their antigen-sensitive cells stimulated locally by the passaged antigen; (3) provision of a special milieu for generation of more secondary' IgA precursor cells; (4) release of IgA precursors which rapidly become non-recirculating IgA-immunoblasts and lodge in mucosal and exocrine tissue; and (5) release of long-lived, recirculating IgA precursors that can contribute to 'local' secretory immunity at a distant site upon subsequent exposure to antigen there. One overall objective of this project has been to determine how 'environmental' antigens, maternal antibodies passively acquired perinatally, deliberate infections via a mucosal route or deliberate exposure of mucosae to macromolecular, non-living antigens may influence the population of lymphoid cells in murine mucosal follicles and hence prejudice a subsequent secretory, IgA-antibody response by the mouse. A second major objective is to elucidate the molecular bases for (a) sessile-motile transitions occurring in mucosal follicles to release specific lymphoid cells into the circulation; (b) for the restriction of these cells to certain recirculation pathways and to certain blood-tissue egress sites; and (c) for the selective lodging of IgA cells in mucosal or exocrine tissue. A third general objective of our studies is to identify the B-cell/T-cell interactions relevant to the expression and control of a mucosal IgA response and to define the pertinent in vivo sites where these interactions may occur. A final main onjective is to understand, in general, how mucosal follicles come to accumulate such relatively high frequencies of IgA precursor cells of certain specificities and, in particular, the molecular mechanisms operative during the process of B-cell differentiation leading to a commitment to IgA expression.
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