Histamine induced murine suppressor and potentiating factors

Mouse spleen cells were incubated for 24 hours in the presence of histamine (10(-13)-10(-3) M). Aliquots of the histamine free supernatants were intravenously injected into either syngenic or allogenic mice which were subsequently analysed by the Jerne plaque assay in respect of their specific IgM response against red blood cells from sheep. Depending on the histamine concentration during the preincubation and the mouse strain, the effects of the supernatants were found to be suppressive or potentiating. Both the histamine induced suppressor and potentiating factor are generated by T-cells and can be precipitated by (NH4)2SO4. These precipitates were fractionated by gel filtration which revealed a molecular weight of both factors in the range of 20 to 50 kDa. Both lymphokines were found to be sensitive to trypsin, low pH, and heat treatment but were not affected by neuraminidase. They do only interfere with the early events of the IgM response within 24 hours after the administration of the antigen. The conclusion is that the bidirectional modulation of the humoral immune response by histamine in mice is partially due to the induction of these lymphokines by a different efficacy of the histamine receptor activation at different T-cell subsets.