The frequent expansion of a subpopulation of B cells that express RF-associated cross-reactive idiotypes: evidence from analysis of a panel autoreactive monoclonal antibodies.

Preferential expression of VH gene segments is evident within the adult human primary B-cell repertoire. The repertoire may be influenced by genetic factors, e.g. VH gene segment polymorphisms, or in a temporal manner due to the exposure to environmental antigens. The molecular characteristics of 15 autoreactive human monoclonal antibodies (MoAbs) are reported. All antibodies were of the IgM isotype, and 12 of the 15 were polyreactive and included rheumatoid factor type specificity, i.e. reactivity with IgG. Nine of the 15 MoAbs are products of VH3 gene segments, as evidenced by staphylococcal protein A binding; four of these express the cross-reactive idiotype recognized by the mouse MoAb 3H7 and are thus products of the VH26 gene segment. One of the five remaining VH3 gene products expresses the cross-reactive idiotypes recognized by the mouse MoAbs B6 and D12. V-gene family usage, determined by polymerase chain reaction (PCR) amplification of cDNA and further hybridization with family-specific oligonucleotide probes, confirmed the cross-reactive idiotype studies and showed that only VH3-gene-encoded proteins bound staphylococcal protein A. Five of the six non-VH3 gene segment products express the cross-reactive idiotype recognized by the mouse MoAb LC1 and could be assumed to be products of the VH4.21 gene segment; however, one human MoAb is shown to be the product of a VH2 gene segment. This is interesting because it turns LC1 from being an anti-cross-reactive idiotype antibody into an anticlan reagent.