The immunoglobulin VH gene, VH4-21, specifically encodes autoanti-red cell antibodies against the I or i antigens.
Most autoanti-red cell antibodies found in patients with cold agglutinin disease are specific for the I or i carbohydrate antigenic determinants. However, antibodies specific for other antigens such as Pr or Sa can also be found, and these are identified by their pattern of reactivity with enzyme-treated red cells. Recently, it has been shown that the vast majority of anti-Ii antibodies react with a monoclonal anti-idiotypic antibody (9G4); this reactivity arises from restriction of the immunoglobulin heavy chains used to encode the antibodies to a single VH4-21 gene, VH4-21. The 9G4 antibody appears specific for this gene product, and we have used it to analyse VH4-21 gene involvement in encoding a spectrum of red cell antibodies of various specificities. The results support the strong association between usage of this gene and anti-Ii specificity and indicate that it is not generally used by other specificities. In particular, it is striking that the unsubstituted type 2 oligosaccharide antigens (I and i) induce a highly restricted autoantibody response very different from that induced by the sialylated type 2 antigens (Sia-b, -1 and 1b). The 9G4 antibody therefore provides a simple tool for discrimination between these autoanti-red cell antibodies, which should be of use in red cell serology.
Smith
G
G
Wessex Blood Transfusion Centre, Tenovus Laboratory, Southampton, UK.
Spellerberg
M
M
Boulton
F
F
Roelcke
D
D
Stevenson
F
F
D000328:Adult; D000373:Agglutinins / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D003450:Cryoglobulins; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004912:Erythrocytes / Q000276:immunology*; D005803:Genes, Immunoglobulin; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007048:I Blood-Group System / Q000235:genetics* / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology
D000373:Agglutinins; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D003450:Cryoglobulins; D007048:I Blood-Group System; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; C029443:cold agglutinins