INDUCTION OF IGE AND IGG1 IN HUMAN B-CELL CULTURES WITH STAPHYLOCOCCAL SUPERANTIGENS - ROLE OF HELPER T-CELL INTERACTION, RESISTANCE TO INTERFERON-GAMMA

Non-antigen-specific activation of human B lymphocytes for IgE product ion in vitro requires the presence of interleukin 4 and non-cognate ph ysical interaction with T cells. The latter can be replaced by antibod ies directed against the B cells' CD40 structure. Antigen-specific ind uction of immunoglobulin responses, including IgE, is difficult in hum an lymphocyte cultures. Thus, we developed a model system which might resemble physiological B lymphocyte stimulation by antigen. Co-culture s of purified tonsillar B cells from normal donors with non-HLA matche d T helper clones obtained from the skin of atopic dermatitis patients produced significant levels of IgE and IgG1 after stimulation with ap propriate types of staphylococcal exotoxins, provided that IL-4 was al so induced in the T cells. Such responses were further enhanced by add ition of low doses of anti-CD40 antibodies. Concentrations of anti-CD4 0, optimal for stimulation of B cells in the absence of T helper lymph ocytes, were less effective in this regard and even inhibitory in some experiments. Most powerful immunoglobulin induction was observed when the cultures were spiked with low amounts of IL-4 and anti-CD40 which did not elicit substantial immunoglobulin production in the absence o f the staphylococcal exotoxins. Induction of IL-2 in T/B cell cultures by superantigens without production of appreciable quantities of IL-4 provoked considerable IgG1 titer but no IgE. High amounts of interfer on-gamma generated by the T cells in vitro in the presence of superant igens did not appear to interfere with immunoglobulin induction. Addit ion of recombinant interferon at the beginning of the culture period a t doses which effectively suppressed IL-4 plus anti-CD40 induced immun oglobulin responses did not inhibit T helper and superantigen dependen t B cell activation. Superantigen mediated B cell stimulation for immu noglobulin production was dependent on cell-cell contact. The experime ntal results presented suggest that this cellular interaction did not necessarily involve T-B cell bridging by superantigens.