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 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-sequencing 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.
Chastagner
P
P
Institut Pasteur, Paris, France.
Demaison
C
C
Thèze
J
J
Zouali
M
M
D000328:Adult; D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000235:genetics*; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region