The syngeneic lymphcyte reaction (SMLR) represents a proliferative response of T-cells to syngeneic non-T cells and appears to be analogous to the autologous mixed lymphocyte reaction (AMLR) in humans. AMLR occurs in normal individuals but is absent in patients with chronic lymphocytic leukemia and systemic lupus erythematosus. SMLR is found in all strains of mice except NZB, which have an autoimmune phenotype associated with antibodies to thymocytes and to DNA. My research objectives are to 1. determine the functional significance of SMLR and the nature of the responding and stimulating cells, 2. investigate the SMLR defect in NZDB mice and determine the relationship to naturally occurring thymocyte antibody (NTA) in these animals, and 3. perform genetic analysis of SMLR and NTA. Data on the functional significance and nature of the cells involved in SMLR will be provided by studies on cell surface markers such as Ly antigens of the responding and Lyb antigents of the stimulating cells and the effects of SMLR-activated T-cells on in vitro and in vivo reponses of B-cells. SMLR done after adult thymectomy, cyclophosphamide treatment, immunization of syngeneic mice with SMLR activated T-cells and after immunization with T-independent and T-dependent antigens will further define the cells involved. Correlation of SMLR and NTA in individual NZB mice and the effect of NTA plus complement treatment on SMLR responder cells in non-immune strains will provide information regarding the relationship of these two phenomena. Finally, the use of recombinant-inbred strains of mice derived from NZB and C58 parentage (NX8 lines) will allow genetic analysis of SMLR and NTA. The strain distribution patterns (SDP) of SMLR and NTA will be compared to the known SDP of a variety of immunologically relevant characteristics. The overall hypothesis forming the basis for these studies is that SMLR reflects an immunoregulatory mechanism and that its absence in NZjB mice may mean a relationship to the pahognesis of autoimmune disease.