THE IMMUNOGLOBULIN-V-H GENE, V(H)4-21, SPECIFICALLY ENCODES AUTOANTI-RED CELL ANTIBODIES AGAINST THE I OR I ANTIGENS

Most autoanti-red cell antibodies found in patients with cold agglutin in disease are specific for the I or i carbohydrate antigenic determin ants. However, antibodies specific for other antigens such as Pr or Sa can also be found, and these are identified by their pattern of react ivity with enzyme-treated red cells. Recently, it has been shown that the vast majority of anti-Ii antibodies react with a monoclonal anti-i diotypic antibody (9G4); this reactivity arises from restriction of th e immunoglobulin heavy chains used to encode the antibodies to a singl e V(H)4-21 gene, V(H)4-21. The 9G4 antibody appears specific for this gene product, and we have used it to analyse V(H)4-21 gene involvement in encoding a spectrum of red cell antibodies of various specificitie s. The results support the strong association between usage of this ge ne and anti-Ii specificity and indicate that it is not generally used by other specificities. In particular, it is striking that the unsubst ituted type 2 oligosaccharide antigens (I and i) induce a highly restr icted autoantibody response very different from that induced by the si alylated type 2 antigens (Sia-b, -1 and 1b). The 9G4 antibody therefor e provides a simple tool for discrimination between these autoanti-red cell antibodies, which should be of use in red cell serology.