These studies are aimed at developing a more complete understanding of the origin and functional significance of murine T lymphocytes that have surface membrane Fc receptors. In previous studies, we established that BALB/c mice with subcutaneous plasmacytomas develop large numbers of circulating T lymphocytes that express surface membrane receptors for the heavy chain isotype of the myeloma protein. Since the initiation of this project, we have further established that the myeloma protein induces an expansion of pre-existing T cells with Fc receptors and that this response to the myeloma protein appears to be an exaggerated but otherwise normal immunoregulatory response. The T-alpha cells induced by IgA myeloma protein are Lyt 1?-?2?+? cells that can function as IgA-specific suppressor cells in vivo. Ongoing studies address the mechanisms by which monoclonal immunoglobulins induce the expansion of FcR-bearing lymphocytes, as well as the biochemical events that underlie the lgA-specific suppression. T-alpha cell-enriched normal lymphocytes as well as cloned lines of T-alpha cells have been shown to suppress the secretion of myeloma protein in vitro in an isotype-specific fashion. Studies are addressing the biochemical events that occur within the suppressed myeloma cells coincident with the cessation of immunoglobulin secretion. Studies are addressing the mechanisms that regulate the expression of IgA-Fc receptors on T cells and the relationship of the expression to the functional state of the T cell. Hybridomas that co-express and secrete two monoclonal proteins are being used to examine the specificity of suppression. Isolation and chemical characterization of the IgA-Fc receptor are being carried out using a T cell lymphoma that expresses IgA-Fc receptors. These studies are aimed at identification of the structural basis of IgA binding to T cells and to a determination of the immunoregulatory functions of T alpha cells in normal hosts and in hosts bearing plasmacytomas. In the past year we have shown that mice with an IgE hybridoma develop large numbers of suppressor T cells that express IgE Fc receptors, and that IgG and IgM producing tumors evidence increased numbers of T and T cells, respectively. We have identified syngeneic T cell lymphomas that express IgM and/or IgG receptors and are attempting to clone the gene for the IgA Rc receptor expressed on a clone of T lymphoma cells. (AB)
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