Rearrangement of the human heavy chain variable region gene V3-23 in transgenic mice generates antibodies reactive with a range of antigens on the basis of V(H)CDR3 and residues intrinsic to the heavy chain variable region

To formulate a 'logic' for how a single immunoglobulin variable region gene generates antibodies with different antigen specificity and polyreactivity , we analysed chimeric antibodies produced in transgenic mice carrying the germ-line human V3-23 gene, multiple diversity (D) and joining (J) gene seg ments. Hybridomas producing antibodies encoded by the V3-23 gene in combina tion with different mouse V-kappa genes were obtained by fusion of splenocy tes from transgenic mice. All antibodies had human mu -chains and mouse lig ht chains, were multimeric in structure and expressed the human V3-23 gene. Nucleotide sequence analyses of genes encoding the heavy and light chains of 12 antibodies in relation to antigen specificity highlighted the importa nce of heavy chain variable region CDR3 in determining reactivity with diff erent antigens. However, the results also suggest that non-CDR3 sequences i ntrinsic to the V3-23 gene itself may be involved in, or determine, the bin ding of the chimeric antibodies to some of the antigens tested in the curre nt study.