This research studies the mechanism of the isotype-specific suppression mediated by the T cells with Fc receptors found in mice with myeloma. We have previously shown that mice and patients with myeloma develop an increase in T cells with surface-membrane Fc receptors. Recently, we have found that the T cells with IgA-Fc receptors in IgA myeloma are isotype-specific suppresser cells. We, herein, propose to utllize normal immune response models to study the effects of T cells with IgA-Fc receptors (T-alpha cells) isolated from mice with IgA myeloma on: (1) the immunoglobulin isotype switch from mu to alpha; (2) the clonal expansion of IgA-committed B cells; (3) the differentiation of IgA committed B cells to secretory plasma cells; (4) the secretion of IgA plasma cells, and (5) their effects on other immunoregulatory T cells. We also intend to utilize MOPC-315 as an IgA myeloms-tumor model to study the effects of T-alpha cells on: (1) clonal growth of MOPC-315; (2) MOPC-315 tumor cell survival; (3) differentiation of MOPC-315; and (4) immunoglobulin production and secretion by MOPC-315. We also intend to iaolate and characterize any soluble-suppressor factors that are released by T-alpha cells found in mice with IgA myeloma cells. Finally, in order to confirm the generality of isotype-specific suppressor cell generation in myeloma, we will extend our studies of T-alpha cells and utilize similar models of normal immune responses and myeloma tumor models to study T-gamma cells in IgG myeloma and T-mu cells in IgM myeloma. The information generated from these studies is likely to: (1) contribute further to our understanding of the host response to myeloma that may ultimately lead to the development of specific immunotherapeutic strategies for the treatment of myeloma and related disorders; and (2) contribute to our understanding of the regulation of isotype expression during normal immune responses. (LB)
