Human monoclonal anti‐D antibodies: II. THE RELATIONSHIP BETWEEN IgG SUBCLASS, Gm ALLOTYPE AND Fc MEDIATED FUNCTION

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Abstract
Summary. Eight monoclonal antibodies (mabs) to the Rh antigen D produced by Epstein‐Barr virus transformed Blymphoblastoid cell lines from two indivbduals have been compared for their behaviour in in vitro cell‐mediated assays. Three IgGl Glm(1.17) and two IgG3 G3m(21) mabs from one donor and three IgGl Glm(3) mabs from another were used. IgG3 anti‐D mabs induced greater adherence and phagocytosis of sensitized red cells by U937 monlocytes than IgGl anti‐D mabs or the polyclonal anti‐D. Minimum sensitization levels for rosetting and phagocytosis by 1393 7 monocytes were 2000 molecules IgG/cell for IgG3 and 5000 molecules/cell for IgGl mabs; maximum rosetting mediated by both IgGl and IgG3 mabs was obtained at 15000‐20000 molecules/cell. The IgG3 anti‐D mabs weire comparable to polyclonal anti‐D in mediating binding of sensitized red cells to γ‐interferon stimulated monocyte‐derived cultured macrophages and were markedly more effective than the IgGl anti‐D mabs. However, in lymphocyte ADCC assays, only anti‐D mabs which were IgGl Glm(3) were effective in mediating high levels of lysis of sensitized red cells, unlike the IgGl Glm (1.17) or IgG3 G3m(21) mabs. Minimum sensitization levels required for this lymphocyte‐mediated red cell lysis were found to be approximately 5000 molecules/cell with one IgGl Glm(3) mab; maximum lysis with this mab was obtained at 10000 molecules/cell. Polyclonal anti‐D containing both IgGl and IgG3 was effective in all three assays. These observations suggest that different isotypes and allotypes of anti‐D antibodies mediate red cell remo or destruction by monocyte or lymphocyte effector ce’through functionally dissimilar Fc receptor interactions.