INDUCTION OF IGE AND IGG1 IN HUMAN B-CELL CULTURES WITH STAPHYLOCOCCAL SUPERANTIGENS - ROLE OF HELPER T-CELL INTERACTION, RESISTANCE TO INTERFERON-GAMMA
D. Armerding et al., INDUCTION OF IGE AND IGG1 IN HUMAN B-CELL CULTURES WITH STAPHYLOCOCCAL SUPERANTIGENS - ROLE OF HELPER T-CELL INTERACTION, RESISTANCE TO INTERFERON-GAMMA, Immunobiology, 188(3), 1993, pp. 259-273
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.