Suppression of Hybrid Myeloma Cells

Humoral immune responses are known to be regulated, both positively and negatively, by antigenand idiotype-specific T lymphocytes. Despite the large body of evidence supporting this notion (1-3), the mechanisms by which T cells influence B lymphocyte differentiation and function are largely unknown. One of the major reasons for this is the vast heterogeneity of the immune system, so that only very few lymphoid cells in an individual are committed to recognizing and responding to any defined antigenic determinant. As one approach to investigating the regulation of B lymphocytes and antibody secreting cells, we, as well as others, have focused on the development of antigen-specific myelomas as model systems for lymphoid cells because such homogeneous tumor lines are amenable to detailed biochemical and morphologic analyses (4, 5). It is now established that the function of myeloma cells can be regulated by tolerogenic antigens and immune complexes (6, 7), carrier-specific helper and suppressor T cells (8), idiotype-reactive T lymphocytes (9-11), and haptenspecific cytolytic T cells (12). Recently, we have described two types o f T cells that specifically suppress myeloma function in vitro. The first (10) is an idiotype-reactive suppressor T cell (Ts), a which is induced by immunizing BALB/c mice with syngeneic cells to which the BALB/c myeioma protein, M315 (IgA,~k~), is covalently coupled. Such Ts inhibit antibody secretion by MOPC 315 cells in vitro in the absence of any antigen without affecting cell growth or viability; moreover, these T lymphocytes, similar to Ts in other systems, bear surface determinants encoded by the I-J subregion of the H-2 complex, their precursors are sensitive to cyclophosphamide, and they can be bound to plastic dishes coated with the M315 myeloma protein (10). The anti-idiotypic specificity of these Ts was established by their inability to bind to plastic dishes coated with M460 myeloma protein, which, like M315, binds 2,4-dinitrophenol (DNP) and 2,4,6-trinitrophenol (TNP) but does not share idiotypic determinants with M315. The second type of