title: Human monoclonal antibodies against blood group antigens preferentially express a VH4-21 variable region gene-associated epitope.
abstract: An anti-idiotypic antibody has been raised which recognizes human immunoglobulins with cold agglutinin activity of anti-I/i specificity. The pattern of reactivity of the antibody indicates that the structural basis for the epitope is located in the VH4-21 gene segment of the VHIV family, which is preferentially utilized by these cold reactive antibodies. Using this antibody, epitope expression was investigated in a panel of 72 human monoclonal allo-antibodies specific for human blood group antigens, as compared with a control panel of 39 randomly selected human monoclonal IgM antibodies of unknown specificities. The anti-blood group panel included 44 IgM and 28 IgG monoclonal antibodies against a variety of blood group antigens including the A antigen, Rh C, c, D, E, e, G antigens, and the Kidd antigens Jka and Jkb. The epitope was expressed by 64% (28/44) of the IgM anti-blood group antibodies and by 21% (6/28) of the IgG antibodies, but by only 7.7% (3/39) of the control IgM antibodies. These data indicate that the human alloimmune response to blood group antigens is biased in the use of VH gene families, with a preference for the VH4-21 gene segment of the VHIV family, or closely related gene segments. The fact that this mirrors the findings for the autoimmune cold agglutinins suggests a link in immunoglobulin gene usage between antibodies against structurally diverse antigens on the red cell surface.
authors.affiliation: Department of Biochemistry, Polytechnic of East London, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Thompson
authors.forename: J
authors.initials: J
authors.lastname: Sutherland
authors.forename: G
authors.initials: G
authors.lastname: Barden
authors.forename: M D
authors.initials: MD
authors.lastname: Melamed
authors.forename: I
authors.initials: I
authors.lastname: Randen
authors.forename: J B
authors.initials: JB
authors.lastname: Natvig
authors.forename: V
authors.initials: V
authors.lastname: Pascual
authors.forename: J D
authors.initials: JD
authors.lastname: Capra
authors.forename: F K
authors.initials: FK
authors.lastname: Stevenson
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D015415:Biomarkers; D001789:Blood Group Antigens / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000096:biosynthesis* / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007135:Immunoglobulin Variable Region; D066298:In Vitro Techniques
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D001789:Blood Group Antigens; D000939:Epitopes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region