Molecular signatures of anti-nuclear antibodies: contributions of specific light chain residues and a novel New Zealand Black V kappa 1 germline gene.
Although the Ig H chains of anti-nuclear Abs (ANA) have been described to possess certain shared molecular signatures, it remains unclear whether the L chains of these Abs also possess distinctive molecular features. The present study examines this by generating and analyzing two comprehensive murine Ig L chain databases, one consisting of 264 monoclonal ANAs and the other consisting of 145 non-ANAs, drawn from previously published work. Importantly, clonal replicates were represented only once each, so as to minimize bias. ANAs and non-ANAs did not differ in Vkappa family or Jkappa gene usage, nor in their mutation frequencies. Interestingly, the L chains of ANAs exhibited differential usage of certain complementarity-determining region residues, arising almost entirely from the increased usage of certain Vkappa germline genes, notably, Vkappa ai4 among anti-dsDNA ANAs, Vkappa23-45 among anti-ssDNA ANAs, and Vkappa21-12 among non-ANAs. Finally, prompted by the increased prevalence of a particular Vkappa1 family sequence among ANAs, we proceeded to clone a novel New Zealand Black Vkappa1 germline gene, named bb1.1, which appears to be frequently used to encoded anti-ssDNA Abs. Collectively, these studies underline the potential contribution of particular Vkappa germline genes in promoting or thwarting DNA binding.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D000916:Antibody Diversity / Q000235:genetics; D004277:DNA, Single-Stranded / Q000276:immunology; D030541:Databases, Genetic; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D007133:Immunoglobulin Joining Region / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008814:Mice, Inbred NZB; D009154:Mutation; D009707:Nucleosomes / Q000276:immunology
D000974:Antibodies, Antinuclear; D004277:DNA, Single-Stranded; D007133:Immunoglobulin Joining Region; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D009707:Nucleosomes