We will define as precisely as possible structural and functional properties of accessory cells which participate in several kinds of immunoregulatory activities. Improved methodology will be developed for preparing accessory cells from mouse spleen, free of contaminating lymphocytes. Accessory cell subpopulations distinguished on the basis of surface markers (Ia, K/D, Fc, C), physical properties (propensity to adhere, size) and general biological properties (sensitive to steroids and/or irradiation, phagocytic ability) will be created and studied in immunoregulatory assays. These assays include the production of several distinct regulatory factors and the ability to process and present immunogens to different T cell subsets. The accessory cell lesions of NZB mice will be investigated in detail and the relationships of these to T cell lesions of NZB mice will be further characterized. These studies may lead to more fundamental understanding of the cellular basis of pathophysiology in lupus erythematosis, rheumatoid arthritis and related diseases. The principal methods to be employed in this project include: 1) Immunizing cultured mouse spleen cells; 2) Measuring immune reactions by proliferative, humoral and cytotoxic assays 3) Separating cells with an improved rosette depletion technique; 4) Generation and testing of accessory cell mediators which affect various specific lymphocyte functions; and, 5) Producing and analyzing the structural and functional characteristics of cloned, normal accessory cells.