Immune mechanisms may play a significant rgle in the etiology and pathogenesis of gastrointestinal disease (e.g., inflammatory bowel disease). Although Peyer's patch and lamina propria tymphoid cells comprise the 2 major lymphoid populations of the small intestine, their function is poorly understood. I propose to examine the induction of immune responses in intestinal lymphoid cells and characterize the relationship between the Peyer's patch and lamina propria lymphoid populations. In initial studies, Peyer's patch lymphocytes could be cultured in vitro. Culture conditions will be manipulated (e.g., thymus-dependent and thymus-independent antigens, mitogens, addition or depletion of T cells and/or macrophages), to define Peyer's patch lymphocytes in functional terms (e.g., B cells, T cells, macrophages) and to determine the requirements for immune induction of Peyer's patch precursor antibody-forming cells (P-AFC). The majority of lamina propria antibody-forming cells (AFC) produce IgA. Since lamina propria AFC's appear to be derived from Peyer's patch P-AFC's, I will determine iD P-AFC's isolated directly from Peyer's patches can be induced in vitro to express selectively the IgA class. Furthermore, since T cells may be essential to switching from IgM to IgG and IgA responses, syngeneic and allogeneic T cells as well as lipopolysaccharide (i.e., B cell mitogen acting as T cell substitute) will be used in these cultures. Conversely, Peyer's patch lymphocytes may become committed to IgA expression only after migration to the lamina propria (e.g., local hormonal effect). Therefore, the distribution kinetics and immunoglobulin class expression of Peyer's patch cells will be examined in vivo under normal conditions (i.e., in the absence of allogeneic stimulation and a lethally irradiated host). The final objective of this study is to apply in vitro microculture methods to lamina propria lymphoid cells and examine immune induction in this cell population. The methods used to study astrointestinal lymphoid function in mice, should serve as a model for investigations of human gastrointestinal lymphoid function.