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 lb). 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.