In aged subjects with no demonstrable disease, the incidence of autoantibodies is increased. In spite of intensive investigation of the triggering, inactivation and regulation of immunocompetent cells, the subcellular mechanisms operative in these phenomena remain poorly understood. One of the central problems in analyzing such events is the vast heterogeneity of the immunocompetent cells in antigen specificity and in immunological functions. Attempts to enrich homogeneous immunocompetent cells on the basis of antigen specificity and function have met with only limited success to date. Thus, it would be important to develop monoclonal cell lines of immunocompetent cells in order to investigate the regulation of specific immune responses which are related with disease processes, such as autoimmune disorders, allergy and immunodeficiency disease. The following areas will be investigated: (1) I propose to develop auto-antibody producing hybridoma cell lines from immunocompetent cells of aged subjects; (2) I propose to study the generation of antigen-specific suppressor factors capable of suppressing autoantibody production by hybridoma cell lines; (3) I propose to study the regulation of autoantibody synthesis by the hybridoma cell lines by suppressor cells or by suppressor factors generated by the suppressor cells; (4) I propose to examine the hypothesis that the suppressor cells interact with the autoantibody producing hybridoma via an anti-idiotype-idiotype interactions. The molecular mechanisms of suppression will be studied.
