In vitro stimulation of IgE production at a single precursor level by human alloreactive T helper clones.

Human alloreactive proliferating T cell clones were isolated by a combination of allogeneic stimulation and interleukin 2-dependent growth. When cultured with B cells and macrophages bearing the appropriate alloantigens, the helper clones induced the production of high levels of IgE, while in the absence of the appropriate stimulation B cells produced undetectable IgE levels. Allogeneic peripheral blood T cells did not provide any help, but rather suppressed the IgE production induced by the alloreactive clones. The development of culture conditions where the help provided by specific T cell clones is non-limiting and suppressor-cytotoxic T cells are absent allowed the set up of limiting dilution experiments to determine the frequency of the B cells activated to high rate IgE production. One in 2,200-6,000 B cells in the peripheral blood of normal donors was activated to produce measurable amounts of IgE. This experimental system will allow the clonal analysis of the IgE antibody repertoire, in different physiological and pathological conditions.