Genetic analysis of the variable region genes encoding a monospecific human natural anti-DNA antibody.
Recent evidence suggests that natural autoantibodies may play an integral role in the development of the normal immune repertoire. To explore the genetic origins of these antibodies, we have isolated and sequenced the variable (V) region genes encoding both the heavy (H) and light (L) chains of a natural anti-DNA antibody, Kim11.4. The genes appear to be derived from the VH4.18 (subgroup VHIV), JH5, Hum1L1 (subgroup V lambda I) and J lambda 3 germline genes. The origin of the H chain diversity gene is more obscure, being potentially derived from one or more of several germline genes, arranged in either the forward or reverse orientations. Both the Kim11.4 VH and VL genes share significant degrees of similarity with those utilized in other autoantibodies, indicating that at least some degree of V restriction may exist in human autoreactive B cells. The pattern of nucleotide differences between the Kim11.4 VH and VL genes and their putative germline counterparts suggests that the Kim11.4 genes may have undergone somatic mutation and arisen as a result of antigen selection.
Daley
M D
MD
Department of Medicine, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Ontario, Canada.
Misener
V
V
Olee
T
T
Chen
P P
PP
Siminovitch
K A
KA
D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000032:analysis*; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D015723:Gene Library; D005803:Genes, Immunoglobulin; D005854:Germ Cells / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region