IGE VERSUS IGG4 PRODUCTION CAN BE DIFFERENTIALLY REGULATED BY IL-10

Allergen-specific IgE plays a key role in the physiopathology of aller gic disorders, This IgE response is usually accompanied by a productio n of IgG4, Indirect evidence suggests that IgG4 may not be a sensitizi ng Ab but, in contrast, could be protective, As such, it may be of pot ential therapeutic interest to selectively modulate IgE vs IgG4 produc tion, To date, IgE and IgG4 switching seems to be controlled by common mechanisms, We report here that IL-10 has a differential effect on Ig E vs IgG4 production by PBMC, IL-10 decreases epsilon transcript expre ssion 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-induce d IgE switching, In contrast, if added later on B cells that are alrea dy IgE switched, IL-10 potentiates IgE production, Interestingly, what ever the time of addition, IL-10 augments IL-4-induced gamma 4 transcr ipt expression and IgG4 production, with a maximal effect when added d uring the first 3 days, As IL-10 is not a switch factor for IgG4, it i s likely that IL-10 enhances IgG4 production by potentiating IL-4-indu ced IgG4 switching. However, IL-10 may also act by enhancing the growt h and/or differentiation of cells that are already IgG4 committed, Fin ally, 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 suggest ing the existence of a pathway(s) selectively controlling their produc tion.