Previous findings have shown that in patients with rheumatoid arthritis (RA there is a higher than normal mean titer of antibody against a B-cell antigen (RANA) found only in lymphocytes infected by EBV, and that RA blood lymphocytes spontaneously yield in culture a high frequency of B cell clones carrying EBV DNA. We will examine the possibility that there is in RA a disorder involving an abnormal balance between endogenous EBV and its suppression by the immune system. Our studies will examine the characteristics of an 80,000 D EBV-related antigen detected in WI-L2 nuclear extracts with an anti-RANA serum and determine whether it corresponds to RANA immunologically. An attempt will be made to prepare a monoclonal antibody to it and develop an ELISA assay for both RANA and anti-RANA. With the ELISA assay we will determine the kinetics and quantity of RANA generated in normal and RA B lymphocytes. We will determine whether EBV-associated antigens are present in the tissues and fluids of patients with RA using a panel of EBV-related monoclonal antibodies and determine whether these antigens are incorporated into joint fluid or circulating rheumatoid factor (RF) complexes, either in solution or on the surface of leukocytes. Comparison with the normal autoantigens, DNA, Ia, RNP, and Sm will also be made. Serial studies will determine whether there is a variation in the amount of such antigen in RF complexes, that this is associated with variation in disease activity. To investigate the possibility of an abnormal regulation of the outgrowth of EBV-infected B cells, we will assay by limiting dilution the precursor frequencies of natural killer cells (NK) and HLA-restricted cytotoxic T lymphocytes (CTL), Interleukin-2 or interferon secreting cells directed against autologous EBV-infected B cells in normal and RA peripheral blood as compared to control subjects. In all these studies, a comparison will be made of the cells and tissues of control patients with other rheumatic disease or infectious mononucleosis.