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Geneva Biomedical Research Institute, Immunology Department, Glaxo Wellcome Research and Development SA, Geneva, Switzerland
Allergen-specific IgE plays a key role in the physiopathology of
allergic disorders. This IgE response is usually accompanied by a
production of IgG4. Indirect evidence suggests that IgG4 may not be a
sensitizing Ab but, in contrast, could be protective. As such, it may
be of potential therapeutic interest to selectively modulate IgE vs
IgG4 production. To date, IgE and IgG4 switching seems to be controlled
by common mechanisms. We report here that IL-10 has a differential
effect on IgE vs IgG4 production by PBMC. IL-10 decreases 
transcript expression and IgE production induced by IL-4 when added
during the first 3 days of in vitro culture, suggesting that IL-10
decreases IL-4-induced IgE switching. In contrast, if added later on B
cells that are already IgE switched, IL-10 potentiates IgE production.
Interestingly, whatever the time of addition, IL-10 augments
IL-4-induced 
4 transcript expression and IgG4 production, with a
maximal effect when added during the first 3 days. As IL-10 is not a
switch factor for IgG4, it is likely that IL-10 enhances IgG4
production by potentiating IL-4-induced IgG4 switching. However, IL-10
may also act by enhancing the growth and/or differentiation of cells
that are already IgG4 committed. Finally, CD40 ligation reverses the
early down-regulating effect of IL-10 on IgE production. These results
are the first evidence of a molecule that differentially regulates IgE
vs IgG4 production, thereby suggesting the existence of a pathway(s)
selectively controlling their production.
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