INDUCTION AND REGULATION OF IGA RESPONSES IN THE MICROENVIRONMENT OF THE GUT

We have described the development of immune responses induced by antigen uptake and processing in the gut with special reference to the local environment. A model of these immune reactions is given (Fig. 1). Antigen can be taken up in PP via M cells in the epithelium overlying the lymphoid mass. M cells transport the antigen to the dome area where it is processed by macrophages. Dendritic cells and possibly also the macrophages present the antigen to CD4+ Th cells, which in turn stimulate mIgM+ B cells in the corona to switch toward mIgA expression. Follicular dendritic cells are thought to support this specific isotype switch. The generated mIgA+ B cells then migrate to the germinal centers where CD4+ Th cells and follicular dendritic cells promote proliferation of the B cells and the generation of mIgA+ memory B cells. The mIgA+ B cells migrate, eventually after restimulation, to the mesenteric lymph node and via lymph and blood circulation to the lamina propria of the gut where terminal differentiation into IgA-producing plasma cells takes place. Antigen that is taken up through the villus epithelium encounters CD8+ intraepithelial T cells as well as macrophages and CD4+ T cells in the lamina propria of the villi. The macrophages may suppress the induction of immune responses aspecifically. Dendritic cells present the antigen to T cells. Antigen-activated CD8+ and CD4+ T cells migrate to the mesenteric lymph nodes where CD4+ T cells stimulate the switch of mIgM+ B cells toward IgG, or eventually IgA, while CD8+ T cells suppress switching toward IgG leading to (oral) tolerance. The net result of antigen uptake in the villi will be suppression rather than an immune response. The role of the T cell area of PP is largely unknown. In this compartment CD8+ T cells outnumber CD4+ T cells. When activated by antigen the T cells migrate to the mesenteric lymph nodes where they are considered to stimulate or suppress B cell responses in a way similar to that described for T cells activated in the lamina propria. © 1993 Academic Press, Inc.