The goal of this project, since its inception, has been to characterize the effects of T cells with Fc receptors on the growth and differentiation of myeloma tumor cells. Previous studies have shown that mice and patients with myeloma tumors develop a marked expansion of circulating suppressor T cells that bear on their surfaces isotype-specific Fc receptors. These FcR+ suppressor T cells produce a suppressor factor that binds to immunoglobulin (immunoglobulin-binding factor - IBF). We have shown that this IBF can suppress the growth and differentiation of myeloma tumor cells. IBF binds to surface immunoglobulin on myeloma cells and can suppress proliferation of tumor cells. In addition, IBF can also suppress the transcription of immunoglobulin genes by suppressing the function of immunoglobulin enhancers. Using the murine myeloma, MOPC-315 as a target and IgA-binding factor (IgABF - from T cells with IgA-Fc receptors) we herein propose to study the molecular mechanism of this response and: 1) Examine the effect of IgABF on early activation biochemical events associated with binding of IgABF to surface immunoglobulin on myeloma tumor cells. 2) Identify cis acting DNA sequences, within the immunoglobulin heavy chain enhancer, that are important in modulating the effects of IgABF. 3) Identify trans acting proteins, that bind to the sequences identified in specific aim #2, and modulate the effects of IgABF. These studies will contribute to our understanding of immunoglobulin- binding factors and the immunobiology of myeloma. In addition, these studies will contribute to our understanding of the control of B cell proliferation and the production of immunoglobulin by B cells.
