Molecular characterization of the variable regions of a mouse polyreactive IgG2b antibody with rheumatoid factor activity.
The complete nucleotide sequences of heavy and light chains of a mouse polyreactive IgG2b antibody were determined. This antibody, obtained after primary immunization of BALB/c mice with human lymphoblastoid cells, possess anti-HLA-DR and anti-rheumatoid factor activities and reacts with various self and nonself antigens. The VL and VH segments were found to belong to the VK8 and VH7183 families, respectively. The VH segment shared a high percentage of sequence similarity (95%) with previously described germline genes. The VK segment had 98.9% of sequence similarity with a consensus sequence VK8 of antibodies with anti-phosphorylcholine activity. Furthermore, the framework regions 2 and 3 of the VL segment were very similar to the framework regions 2 and 3 of other antibodies known to possess rheumatoid factor activity. We postulate that during immunization, the presence of HLA-DR antigens selects precursors having configurations similar to that of the germline, and induces some somatic mutations that do not significantly affect antibody polyreactivity.
Sequeira
A
A
Unité d'Immunocytochimie, URA 359 du CNRS, Institut Pasteur, Paris, France.
Avrameas
S
S
Jouvin-Marche
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D003001:Cloning, Molecular; D016384:Consensus Sequence; D005803:Genes, Immunoglobulin; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D012217:Rheumatoid Factor / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D012217:Rheumatoid Factor