Surface immunoglobulins on malignant B cells have idiotypic determinants. In addition to viral antigens, these determinants function as tumor-specific antigens and therefore as target sites for the immune system. We propose to analyze the factors which are essential for tumor-specific humoral antibodies and T cells to suppress myeloma growth in vitro and to determine the heritable and nonheritable phenotypic changes which make tumor cells susceptible or resistant to such immunity. Anti-idiotypic immunity is mediated by different kinds of antibodies and T lymphocytes. We plan to investigate the effects of this immunity on the in vitro growth of the S107 myeloma. We have several culture sublines available which differ in amount of surface immunoglobulin and immunoglobulin secretion. We will use a cloning system to measure effects on cloning efficiency, clone size and rate of growth, and to detect changes in the quantity or the idiotypic specificity of the target antigen secreted. Different classes of antibody will be tested for their ability to stimulate or inhibit tumor cell growth. Similarly, the effects of subpopulations of T cells will also be investigated. Clones that have escaped idiotype-specific immune destruction will be isolated. The frequency of escape variants showing heritably increased resistance to anti-idiotypic immunity will be determined. The mechanisms for the increased resistance will be analyzed. The study of this experimental model is expected to provide useful information for developing specific immunotherapeutic procedures.