The overall goal of this work is to develop an adoptive immunization scheme using SCID mice reconstituted with human peripheral blood lymphocytes to generate antigen-specific human MAbs, SCID mice will be pretreated with cytotoxic agents to give improved levels of early human cell reconstitution. These SCID-hu mice will then be immunized with either sonicated or live Borrelia burgdorferi and human antibody responses monitored. SCID-hu mice producing antigen specific antibodies will be sacrificed and the chimeric tissues transformed with EBV. This step will select out human B lymphocytes from the mixture, activate and transform them. Lymphoblastoid lines producing antigen-specific human antibodies will be stabilized and immortalized by hybridization with a mouse-human heteromyeloma line. It is hoped that this will lead to a general method of human cell immunization and human MAb formation. These HMAbs can be utilized as international standards for clinical diagnostic assays.
