Induction of IgE and IgG1 in human B cell cultures with staphylococcal superantigens: role of helper T cell interaction, resistance to interferon-gamma.

ABSTRACT

Non-antigen-specific activation of human B lymphocytes for IgE production in vitro requires the presence of interleukin 4 and non-cognate physical interaction with T cells. The latter can be replaced by antibodies directed against the B cells' CD40 structure. Antigen-specific induction of immunoglobulin responses, including IgE, is difficult in human lymphocyte cultures. Thus, we developed a model system which might resemble physiological B lymphocyte stimulation by antigen. Co-cultures of purified tonsillar B cells from normal donors with non-HLA matched T helper clones obtained from the skin of atopic dermatitis patients produced significant levels of IgE and IgG1 after stimulation with appropriate types of staphylococcal exotoxins, provided that IL-4 was also induced in the T cells. Such responses were further enhanced by addition of low doses of anti-CD40 antibodies. Concentrations of anti-CD40, optimal for stimulation of B cells in the absence of T helper lymphocytes, 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 of 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 interferon-gamma generated by the T cells in vitro in the presence of superantigens did not appear to interfere with immunoglobulin induction. Addition of recombinant interferon at the beginning of the culture period at doses which effectively suppressed IL-4 plus anti-CD40 induced immunoglobulin responses did not inhibit T helper and superantigen dependent B cell activation. Superantigen mediated B cell stimulation for immunoglobulin production was dependent on cell-cell contact. The experimental results presented suggest that this cellular interaction did not necessarily involve T-B cell bridging by superantigens.