ABSTRACT
Despite the abundance of antibodies developed by murine and rat hybridomas, the methodology to produce chimeric and humanized mouse antibodies, and the apparently limitless potential for the expression of human antibody fragments in prokaryotic vectors, there remains at present only one route to the production of unaltered human antibodies - immortalization of human antibody-secreting cells. Although phage display systems (see Chapters 6 and 7) offer an attractive alternative to cell-derived antibodies, they rely on the random association of heavy and light chains and this will not necessarily reflect the combinations found in B cells in vivo. In addition, in some instances, V region glycosylation can make significant alterations in the binding specificity of antibodies (Wright et al., 1991) and phage-derived antibodies will not be glycosylated. Recently, transgenic mice carrying human immunoglobulin gene loci have been developed (Lonberg et al., 1994) and may provide an alternative route to the human antibody response. However, expression of human antibodies by this method is restricted to the small number of V region genes inserted into these mice and depends on the recruitment of appropriate murine T-cell help.
