Substantial evidence is now available that Peyer's patches (pp)l are a major source of precursors of IgA-secreting plasma cells (1-3). These cells are generated in PP by exposure to antigen-specific or nonspecific stimuli. They then exit the PP, migrate through mesenteric lymph nodes, the thoracic duct, and systemic circulation, and finally localize in secretory tissues, where they differentiate into IgA-producing plasma cells (3). There is also considerable evidence that the IgA-predominant antibody production by PP B cells in gut-associated lymphoid tissues (GALT) is controlled by immunoregulatory T cells, such as class-specific helper and suppressor T cells (4-7). More recently, the existence of another type of regulatory T cell in PP, a contrasuppressor-inducer T cell, has been demonstrated, which suggests that IgA production is also influenced by a contrasuppressor regulatory circuit (8). Thus, immunoregulation of the mucosal immune response appears to be quite complicated.As a new approach to the elucidation of the mechanisms governing IgA production in GALT we have studied the effect of cloned T cell lines on in vitro IgA synthesis. Accordingly, we have established concanavalin A (Con A)-induced cloned T cells from both murine PP and spleen and have determined the ability of these cells to regulate IgA immunoglobulin (Ig) synthesis and secretion by lipopolysaccharide (LPS)-driven PP B cells. In addition, we have analyzed the effect of co-cultured Con A-induced cloned T cells on the surface Ig (sIg) profile of PP and spleen B cells.The data obtained strongly suggest that in murine PP there is a special type of T cell that causes switching of sIgM-bearing B cells directly to sIgA-bearing B cells.

It is now well established that Peyer's patches (pp)l are lymphoid follicles that give rise to cells that are committed to IgA development and that ultimately localize in mucosal areas (1-5). However, the mechanisms governing such commitment are not completely understood. On the one hand, PP B cells and their clonal progeny could represent a class of B cells that secrete IgA, because they are exposed to a particular kind and pattern of specific (antigenic) and/or nonspecific (T cell and/or B cell) stimuli (6, 7); on the other hand, IgA B cells may develop in PP because PP contain Ig class-specific PP T cells that direct PP B cells along certain lines of differentiation (8, 9). Recently, we have provided additional evidence favoring the latter possibility, in that we have obtained T cell clones from PP which are capable of influencing PP B cell differentiation so that it follows a pathway that leads directly from IgM expression to IgA expression (10, 11). However, these IgA-specific T cells (switch T cells) cannot in themselves provide help for terminal differentiation of PP B cells since the effect of the switch T cells is to induce cells to become surface IgA-bearing B cells rather than plasma cells secreting IgA.Newer information regarding immunologic mechanisms governing B cell differentiation of all Ig classes are of relevance to IgA B cell differentiation. In this regard, there are extensive data which indicate that T cells or T cell-derived factors, and/or macrophages or macrophage-derived factors induced by specific and nonspecific stimuli can profoundly affect the proliferation and differentiation of T and/or B cells (12-26). These cells and the factors derived from these cells

To study whether senescence-induced changes in the gut-associated lymphoid tissue (GALT) are mainly quantitative, several parameters were examined in three age groups of BALB/c mice (1-2, 12-14, and 24-28 months old). A substantial senescence-associated decline in the number of lymphoid cells was found in the mesenteric lymph nodes (MLN) and spleen (SPN), and especially in the Peyer's patches (PP), but not in the lamina propria (LP). The distribution of lymphocyte subsets in these tissues was also altered with an absolute reduction of T cells--in particular, a L3T4+ helper/inducer T-cell marker-bearing subset. These changes were most remarkable in PP, followed by MLN. The in vitro proliferative reactivity and the production of each isotype-specific immunoglobulin (Ig) by PP, MLN, and SPN were profoundly affected when T-cell-dependent (Td) B-cell mitogens were used, but minimally affected when T-cell-independent (Ti) B-cell mitogens were used. The isotype-specific Ig content of small-intestinal perfusates was also influenced by aging, but only to a minor extent, as exemplified by a decrease in IgA levels in the fasting condition. Thus, despite the defects in the quantity and distribution of lymphocytes in aged PP and MLN, the finding of little change in the total amount of secreted IgA in aged intestine suggests that gut IgA-mediated luminal immune responses could remain nearly unaltered with senescence. The constancy of intraluminal IgA levels could be of physiological significance in host defense at the gut mucosal surface in aged mice.