A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene.
We report the Ig H and L chain V region sequences from the cDNAs encoding a monoclonal human IgG anti-cardiolipin/ssDNA autoantibody (R149) derived from a patient with active SLE. Comparison with the germ-line V-gene repertoire of this patient revealed that R149 likely arose as a consequence of an Ag-driven selection process. The Ag-binding portions of the V regions were characterized by a high number of arginine residues, a property that has been associated with anti-dsDNA autoantibodies from lupus-prone mice and patients with SLE. The VH gene encoding autoantibody R149 was a somatically mutated variant of the 51P1 gene segment, which is frequently associated with the restricted fetal B cell repertoire, malignant CD5 B cells, and natural autoantibodies. These data suggest that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti-cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted VH genes can give rise to disease-associated autoantibodies through Ag-selected somatic mutations.
Van Es
J H
JH
Department of Immunology, University Hospital Utrecht, The Netherlands.
Aanstoot
H
H
Gmelig-Meyling
F H
FH
Derksen
R H
RH
Logtenberg
T
T
D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000235:genetics*; D001483:Base Sequence; D002308:Cardiolipins / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology*; D015870:Gene Expression; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics
D000974:Antibodies, Antinuclear; D002308:Cardiolipins; D004277:DNA, Single-Stranded; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger