Sequence Analysis and Idiotypic Relationships of BEG-2, a Human Fetal Antibody Reactive with DNA

Monoclonal antibody (mAb) BEG-2 is a dsDNA binding IgM λ derived from a 12-week human fetus. Two binding site idiotypes (BEG-2 Id α and BEG-2 Id β) have been defined with the use of polyclonal rabbit anti-idiotypic anti-serum. BEG-2 Id α is located on the λ light chain and has been described previously. The BEG-2 Id β is present on the μ heavy chain. By means of a direct binding ELISA, BEG-2 Id β has been identified on EBV-derived mAbs from human fetal liver or spleen (5%), human cord blood (2.7%) and adult peripheral blood (1%). In addition, the Id is present on 8.5% of adult spleen-derived hybridoma antibodies and 6% of RA synovium-derived hybridoma antibodies. In all populations the presence of the Id is associated with binding to DNA and other polyanions. Competition indicated that the Id was located at or near the antigen-binding site on these molecules. To explore the structural basis of this binding, a major part of the BEG-2 chain was sequenced and found to be encoded by a member of the VH4 family joined to a variant of JH5 by a very short Diversity or N region. Of the BEG-2 Id β positive mAbs for which the VH family has been determined, five are encoded by VH4 and two are encoded by VH6, but none is encoded by other families. Thus, the BEG-2 Id β identifies a set of polyreactive antibodies that are common in fetal life, into adulthood and are encoded by VH6 and, a subset of VH4 genes.