ABSTRACT

The gene constructs contained variable region genes, diversity segments, joining segments and one or two constant regions for the H chain, and Vs, Js and one C gene for the L chain. The experiments showed rearrangements of the transgenes, leading to a human antibody repertoire, which demonstrated the possibility of eliciting specific human responses after immunisation. Further improvements of the human antibody production in transgenic mice could be achieved by replacing mouse antibody genes, or indeed the mouse Ig loci, with human genes. Successful attempts have been made to replace mouse V and C region genes with aim of using mouse control elements to drive human antibody expression. A comparison of transgenic lines shows that larger, authentic regions lead to better expression which may mean that the addition of more segments or control elements is essential. Human antibody production is most efficient in a mouse knock-out background and this lack of competition resulted in specific human antibody repertoires after immunisation.