Identification and characterization of cellular and molecular factors important in the identification of human neoplastic and normal B cells will be continued in this study. Emphasis will be placed on the B cells at the terminal stages of differentiation. Myeloma cell lines and cryopreserved myeloma cells as well as plasma cells generated in vitro will be utilized to identify surface molecules expressed by plasma cells and/or by B cells at late stages of maturation. Antiserums of both conventional type and generated by hybridoma monocional antibody technology will be utilized to study the expression of these antigens by differentiating B cells. The roles of these antigens in the differentiation scheme of B cells will be ascertained. Myeloma-specific or -associated antigens will be sought. The availability of a newly-established IgD myeloma cell line and its paired B lymphoblastoid lines in our laboratory will facilitate this analysis. The heterogeneity of human B cells will be studied by the further identification of precursor cells for the two types of human B cell colonies. Continued efforts will be made to induce terminal differentiation of chronic lymphocytic leukemic B cells with mitogens, T cell helper factor and other pharmacological agents. Newer markers for terminal stages of B cell differentiation will be utilized. A method will be devised to stimulate leukemic cells to undergo mitosis for further analysis of karyotype abnormality associated with this disorder. Hybridoma antibodies against a minor population of T cells will be defined further. The functional capacity of the reactive population in relationship to B cell differentiation will be determined. Specific helper T cell defect in patients with chronic lymphocytic leukemia will be further defined. Continual efforts will be made to generate human T-T cell hybridomas. Those secreting T cell factors for B cell differentiation and growth will be identified. The delineation of surface antigens characteristic of normal and neoplastic plasma cells and the definition of factors important in the pathogenesis of chronic lymphocytic leukemia may lead to new therapeutic avenues. This is needed, for no effective therapy is now available for these B cell proliferative disorders. On the basic level, new technological advances have made the human lymphocyte system more amenable to analysis and information concerning this system will continue to have implications for other interacting cellular systems.