Clonotypic Dominance and Variable Gene Elements of Pathogenic Anti‐DNA Autoantibodies from a Single Patient with Lupus

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Abstract
This study explores the usage and diversity of the variable gene elements expressed by human lupus antibodies to DNA bearing the 0–81 idiotype, a marker of pathogenic anti‐DNA autoantibodies. Rather than studying DNA‐specific clonotypes from different patients, a panel of idiotype positive anti‐DNA autoantibody‐secreting clones from a single individual were analysed. By cloning and nucleotide‐sequeneing the heavy‐chain variable gene segments, evidence was found for dominance of clonotypic patterns. Also noted was a high rate of diversification among the variable (VH), diversity (Dh) and junctional (JH) gene segments utilized, 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 an affinity‐maturation process that is reminiscent of antigen‐driven immune responses.