Cold agglutinin activity is common among human monoclonal IgM Rh system antibodies using the V4‐34 heavy chain variable gene segment

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Abstract
BACKGROUND: The V4‐34 gene segment is commonly used by human monoclonal IgM alloantibodies against blood group antigens and by cold‐reactive red cell autoantibodies with anti‐I or anti‐i specificity. This study was conducted to determine whether cold agglutinin activity is found among the V4‐34‐encoded alloantibodies. STUDY DESIGN AND METHODS: Fifty‐ four human IgM monoclonal antibodies (MoAbs) against Rh system antigens were tested for cold agglutinin activity against red cells lacking the relevant Rh system antigen and for reactivity with tissue I and/or i antigens using immunohistochemistry. The findings were correlated with the utilization of the V4‐34 segment as determined in an enzyme‐linked immunosorbent assay with an antibody (9G4) that is specific for this gene product and were also correlated with other serologic properties. RESULTS: Of the MoAbs, 59 percent were 9G4‐positive. Of the 9G4‐ positive subset, 16 and 44 percent agglutinated native adult (express I) and cord (express i) cells, respectively, at 4 degrees C; these levels rose to 84 and 94 percent, respectively, with the use of papain‐ treated cells. The red cell antigens recognized at 4 degrees C were cleaved by endo‐beta‐galactosidase, which is consistent with their being I and i. Of the 9G4‐positive subset, 53 percent bound to tissue i antigen. These reactivities were not found among 9G4‐negative MoAbs. Endo‐beta‐galactosidase treatment of red cells enhanced Rh system antibody agglutination by 9G4‐negative MoAbs. CONCLUSION: Anti‐I/i reactivity is common among IgM Rh system MoAbs and is shown only by the V4‐34‐encoded subset. This finding has implications for the use of MoAbs for Rh system typing of blood.