COMPARISON OF PATHOGENIC AND NONPATHOGENIC MURINE ANTIBODIES TO DNA -ANTIGEN-BINDING AND STRUCTURAL CHARACTERISTICS

Three pathogenic and two non-pathogenic NZB/NZW F1 mAbs to DNA were co mpared. Pathogenicity was defined as the ability to induce nephritis i n BALB/c mice. All mAbs were IgG2a or 2b, had high avidity for double- stranded DNA and fixed complement well. All three pathogens expressed idiotype IdGN2. Mice receiving pathogenic mAbs (compared with non-path ogenic) had more glomerular IgG deposits. The unique properties of two of the pathogens were: strong homogeneous staining of Hep-2 nuclei an d the ability to bind (i) nucleosomes, (ii) histone (after mAb complex ed with DNA), (iii) heparan sulfate in renal basement membranes (after complexing with DNA/histone) and (iv) nuclei in vivo. Comparison of n ucleotide and amino acid sequences of the V regions of heavy and light Ig chains showed use of multiple V(H)DJ(H) and V(chi)J(chi) gene fami lies, with representation of several anti-DNA 'families' described by others. Arginine (R) occurred in the CDR2 or CDR3 of V(H) chains in al l pathogens; R was absent in the CDRs of V(H) chains of non-pathogens. Positively and negatively charged AA were more frequent in V(H) CDR o f pathogens than of non-pathogens. We hypothesize that the tertiary st ructure of mAbs determined by V(H) CDR regions permits stronger bindin g to negatively charged antigens (DNA and heparan sulfate) and to posi tively charged molecules (histone) in pathogens compared with non-path ogens.