We have immortalized human B lymphocytes using hybridoma techniques and Epstein-Barr virus transformation. These cells secrete autoantibodies that react with multiple organs. Some of the autoantibodies have been used in affinity columns to isolate and characterize the autonatigens with which they react. Monoclonal anti-idiotypic antibodies against some of the autoantibodies have been made. These reagents have been used to screen sera from patients with various autoimmune disorders to see whether there is any differnce in the levels of autoantibody associated idiotopes. Some of the idiotopes are generally found in all sera and some others appear to be associated with specific autoimmune disorders. Recently we have made anti-anti-idiotypic antibodies. These antibodies are being used to further understand the nature of autoantigens and autoimmune-response, and to study the autoreactive B cell repertoire in humans.