IgE regulation by nematodes: the body fluid of Ascaris contains a B-cell mitogen

Nematode infection of human beings or laboratory animals leads to markedly increased levels of circulating IgE, most of which is not specific to worm antigens. This phenomenon is known to be interleukin-4-dependent, but little is known about the mechanism of activation of the response. In an attempt to elucidate this mechanism, we have used a reductive approach with worm products rather than infections. In a previous article we showed that injection of the body fluid of the nematode Ascaris yields a marked increase in circulating IgE. In this study we demonstrate that the body fluid contains a B-cell mitogen. Incubation with purified splenic B cells with 50 micrograms/ml body fluid yields marked proliferation of B cells, as measured by tritiated thymidine uptake. Similarly, Ascaris body fluid stimulates G0 B cells to enter the cell cycle. T cells are unaffected by the mitogen, and the response is dependent on viable accessory cells. Contamination of Ascaris body fluid or reagents by bacterial lipopolysaccharide has been ruled out as a source of artefactual data. A model is proposed, which suggests that the B-cell mitogen in Ascaris body fluid stimulates polyclonal B-cell activity and that other nematode factors either stimulate the release of interleukin-4 or act in an interleukin-4-like manner to cause class switch to IgE.