Hapten-modified basophils: a model of human immediate hypersensitivity that can be elicited by IgG antibody.

Trimellitic anhydride (TMA) was incubated with human leukocytes to produce leukocytes with trimellityl (TM) haptenic determinants. The basophils in these TM leukocytes released histamine when challenged with human serum containing IgG but no IgE antibodies against TM determinants. Controls of TMA-treated cells exposed to normal human sera or untreated cells exposed to anti-TM sera released no histamine. The most relevant site of TMA modification of the basophil was receptor-bound IgE. This was demonstrated by the marked reduction in histamine release if IgE was removed from the leukocytes before TMA treatment and challenge and also by activation of release from untreated cells by passive sensitization with TM-IgE before challenge. Affinity-purified IgG from an anti-TM serum released much more histamine from TMA-treated cells than did the IgG-poor effluent at similar protein concentrations. These observations suggest a new model of hypersensitivity resulting from human exposure to chemicals capable of combining with autologous proteins. In some individuals this could result in both an immune response to the new determinants without the production of significant quantities of IgE antibodies and hapten modification of receptor-bound IgE on mast cells and basophils. After sufficient antibody was produced, reexposure to the chemical with hapten modification of mast cells or basophils or both could result in mediator release and clinical symptoms. This mechanism may be relevant to immediate-type chemical hypersensitivity reactions in which IgE antibody has not been demonstrated.