title: Immunoglobulin variable region sequences of human monoclonal anti-DNA antibodies.
abstract: OBJECTIVE
  Anti-DNA antibodies are believed to be important in the pathogenesis of systemic lupus erythematosus (SLE). Antibodies that bind specifically and with high affinity to dsDNA are most closely involved in tissue damage. Analysis of the sequences of the variable regions of human monoclonal anti-DNA antibodies is useful in defining the structural features that give rise to these binding properties. This article systematically reviews the evidence derived from such sequences.
  
  
  METHODS
  Previous reviews of this subject have been hampered by incomplete knowledge of the human immunoglobulin variable region repertoire. In this article, the original sequence data from reports of over 50 human monoclonal antibodies (mAb) are reinterpreted by alignment to the most similar alleles of the most similar germline genes. This allows accurate estimation of the site and nature of somatic mutations.
  
  
  RESULTS
  Human IgG monoclonal anti-DNA antibodies generally carry more mutations than IgM. In many cases these have been selected by an antigen-driven process. In many of the more specific, higher affinity dsDNA binders, there is an accumulation of basic residues in the complementarity determining regions. However, many exceptions to this rule exist, particularly among IgM mAb.
  
  
  CONCLUSIONS
  Unlike murine anti-DNA antibodies, these human mAb show little evidence for preferential use of particular V(H), V(K) and V(lambda) genes or families to encode antibodies of this specificity.
authors.affiliation: Centre for Rheumatology, Department of Medicine, University College, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Rahman
authors.forename: D S
authors.initials: DS
authors.lastname: Latchman
authors.forename: D A
authors.initials: DA
authors.lastname: Isenberg
mesh_terms: D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D004247:DNA / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D004247:DNA