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International Immunology, Vol. 12, No. 9, 1337-1345, September 2000
© 2000 Japanese Society for Immunology

Th1 versus Th2 cytokine profile determines the modulation of in vitro T cell-independent type 2 responses by IL-4

Quirijn Vos, Clifford M. Snapper and James J. Mond

1 Departments of Medicine and Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA

Correspondence to: Q. Vos

We have previously demonstrated that stimulation of B cells by multivalent membrane Ig cross-linking, using dextran-conjugated anti-IgD mAb ({alpha}{delta}-dex), in the presence of cytokines, is an in vitro model for T cell-independent type 2 (TI-2) Ig secretory responses. Earlier studies have shown that IL-4 enhances IgM secretion upon stimulation with {alpha}{delta}-dex plus IL-5 and induces IgG1 isotype-switching, without altering the proliferative response to {alpha}{delta}-dex. Here we show that IL-4 can have both stimulatory and inhibitory effects on {alpha}{delta}-dex-induced Ig secretion. Both the kinetics and time of exposure to IL-4, and the nature of the cytokine additions, Th1 versus Th2, determine whether stimulation or inhibition is observed. Preincubation of sort-purified B cells with IL-4 caused a 6- to 8-fold increase in Ig secretory responses to subsequent stimulation with {alpha}{delta}-dex plus IL-1, IL-2 or a combination of both. However, the continued presence of IL-4 during B cell stimulation suppressed responses to all cytokine combinations tested, except for those which included IL-5. Of 11 cytokines tested, only IL-4 showed this dual effect of enhancement and suppression. The stimulatory effect of IL-4 required a minimum of 4 h of preincubation and could be inhibited by the addition of IFN-{gamma}. Thus stimulation of non-MHC class II-dependent T or non-T cells by multivalent antigens to secrete IL-4 may regulate the response to these antigens, such that early and brief exposure of B cells to IL-4 will enhance a subsequent TI-2 response in the presence of Th1-dependent cytokines, while continuous exposure will result in inhibition of the response.

Keywords: B lymphocytes, cellular differentiation, cytokines, Ig secretion

Transmitting editor: Z. Ovary


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