Human Monoclonal Antibodies against Blood Group Antigens Preferentially Express a VH4‐21 Variable Region Gene‐Associated Epitope

TLDR

Antibodies against diverse red‑cell surface antigens appear to preferentially use VH4‑21 gene segments, mirroring the pattern seen in autoimmune cold agglutinins. The authors employed an anti‑idiotypic antibody to probe epitope expression in 72 monoclonal allo‑antibodies against blood‑group antigens and compared the results to a control panel of 39 unrelated IgM antibodies. The epitope was present in 64 % of IgM and 21 % of IgG blood‑group antibodies, but only 7.7 % of control IgM, demonstrating a VH4‑21 bias in the alloimmune response.

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.