T cell regulation of IgA immunoglobulin production in gut-associated lymphoid tissues.

To explore mechanisms of gut-mucosal IgA immune response, we have established Con A-induced cloned T cell lines originating from PP and spleen. These cloned cells expressed Thy-1.2+, Lyt-1+2-, Ia (I-A and I-E) and H-2 (K/D) surface antigens. Cloned T cells derived from PP were found to suppress LPS-induced IgM and IgG synthesis and secretion of co-cultured PP B cells; in addition, whereas the PP cloned T cells did not bring about IgA production, they did cause the appearance of large numbers of cells expressing sIgA. In contrast, cloned T cells derived from spleen had little or no effect on LPS-induced IgM synthesis and secretion by PP B cells; in addition, whereas they did suppress IgG production, they neither brought about IgA production nor the appearance of cells expressing sIgA. These studies provide evidence for the existence of a new type of T cell in PP, a switch T cell, which is able to induce B cells to undergo class-specific switches from IgM to IgA; the PP switch T cells appear to govern the pathway of DNA recombination (or RNA splicing) rather than cellular events resulting in terminal differentiation. Thus, these switch T cells are probably responsible for the fact that PP are a major source of mucosal IgA B cells. In additional studies, we show that post-switch IgA B cells, i.e. cells precultured with PP cloned T cells, have the capacity to undergo terminal differentiation into IgA producing plasma cells. provided they are exposed to helper T cells (uncloned) and an appropriate mitogenic stimulus (staphylococcal protein A). We can conclude, therefore, that the development of PP B cells into IgA-producing plasma cells in gut-associated lymphoid tissues (GALT) appears to require at least two steps: one which involves heavy chain switching to IgA and which is governed by IgA class-specific switch T cells in PP, and one which involves differentiation of post-switch B cells and which is governed by helper T cells in lymphoid tissues outside of PP (such as MLN and spleen).