CLONOTYPIC DOMINANCE AND VARIABLE GENE ELEMENTS OF PATHOGENIC ANTI-DNA AUTOANTIBODIES FROM A SINGLE PATIENT WITH LUPUS

This study explores the usage and diversity of the variable gene eleme nts expressed by human lupus antibodies to DNA bearing the 0-81 idioty pe, a marker of pathogenic anti-DNA autoantibodies. Rather than studyi ng DNA-specific clonotypes from different patients, a panel of idiotyp e positive anti-DNA autoantibody-secreting clones from a single indivi dual were analysed. By cloning and nucleotide-sequencing the heavy-cha in variable gene segments, evidence was found for dominance of clonoty pic patterns. Also noted was a high rate of diversification among the variable (V-H), diversity (D-H) and junctional (J(H)) gene segments ut ilized, with a pattern of mutations indicative of antigenic selection. These features suggest that the clones secreting the lupus pathogenic autoantibodies have been selected over multiple generations through a n affinity-maturation process that is reminiscent of antigen-driven im mune responses.