Human lymphocyte Hybridomas and Monoclonal Antibodies

Abstract

This chapter reviews the accumulating data concerning human monoclonal antibodies and hybridomas. The Epstein–Barr virus (EBV) selectively infects human B lymphocytes that have the CR2 complement receptor on the plasma membrane. Human and marmoset cell lines have been established that spontaneously release infectious viral particles into the culture medium. The addition of EBV-containing supernatants to human B lymphocytes induces cell division and transformation. The EBV-transformed B lymphocytes express the EB nuclear antigen (EBNA), as detected by anticomplement immunofluorescence. The infected cells grow indefinitely in medium lacking exogenous growth factors. Depending on the cell line, EBV transformed human lymphoblasts release immunoglobulins such as IgM, IgG, or IgA into the culture medium. Because EBV-infected B lymphocytes are polyclonal, they must be cloned early to preserve specific antibody production. The hybridoma antibodies may be prepared in unlimited quantities. They bind to antigen uniformly and reproducibly and can mediate a diverse array of biological activities. Murine hybridorna antibodies have provided crucial information concerning immunoglobulin genetics, and immune regulation. The hybridoma reagents have helped elucidate the structure and function of cell membrane components, lymphokines, enzymes, and many trace proteins. For in vivo therapeutic purposes, human monoclonal antibodies should be much superior to mouse immunoglobulins. The chapter emphasizes the special problems that necessarily accompany experiments with people. An attempt has been made to outline possible future directions of human monoclonal antibody research and development.