RESTRICTED VARIABLE REGION GENE USAGE AND POSSIBLE RHEUMATOID-FACTOR RELATIONSHIP AMONG HUMAN MONOCLONAL-ANTIBODIES SPECIFIC FOR THE AD-1 EPITOPE ON CYTOMEGALOVIRUS GLYCOPROTEIN-B

The nucleotide sequences of the variable region genes encoding five different human, high affinity antibodies, specific for the major neutralization determinant (AD-1) expressed by human cytomegalovirus glycoprotein B (gp58/116), have been determined. Three of the five heavy chain variable regions belonged to the small VHV-family, although they combined with a diverse set of light chains (V(kappa)IIIb, VlambdaII and VlambdaIII). The other two antibodies belonged to V-H-families III and IV. One of the VHV-family genes most likely originated from a previously unreported germline gene or allele, since it carries a nine nucleotide insert in framework 1. In addition, V-lambda-genes showed variable homology (77-95%) to known germline sequences, while V-kappa-genes showed high homology (approximately 98%) with their proposed germline origin. Despite the close homology of the V(kappa)IIIb-gene used to express one of the antibodies with its corresponding germline gene, the protein did not strongly express some idiotypes associated with this light chain family. There is, thus, no direct relation between the expression of these crossreactive idiotypes and the use of even modestly mutated light chains belonging to this V-kappa-family, which has been implicated in the development of anti-idiotypic networks possibly inducing autoantibodies, such as rheumatoid factors.