Abstract: The present invention provides a process for the preparation of human monoclonal antibodies from human B cells. According to this process, human antibody-producing B cells are immortalized by infection with an Epstein-Barr virus, or derivative thereof, that expresses Epstein-Barr virus nuclear antigen 2 (EBNA2). EBNA2 function, which is required for immortalization, is subsequently shut off, which results in an increase in antibody production. The invention provides a variety of systems that allow expression of EBNA2 function to achieve immortalization, followed by reduction of EBNA2 expression or function to facilitate antibody production.