Interleukin 3‐3‐dependent potentiation of IgE responsiveness in mouse basophils

Abstract Basophils produce interleukins (IL)‐4 in response to various stimuli and may contribute to type 2 immune responses to various infections and allergens. We found that resting basophils freshly isolated from mice produce IL‐4 in response to IL‐3 but not to high‐affinity Fc receptor (FcεRI) cross‐linking (CL), yet both required the immunoreceptor tyrosine‐based activation motif (ITAM) containing adaptor Fc receptor γ‐chain (FcRγ), while basophils activated in vitro by IL‐3 become responsive to FcεRI CL. Acquisition of responsiveness to FcεRI CL occurred upon infection with Trichinella spiralis or administration of superantigen. Because cultured basophils return to a quiescent state upon starvation with IL‐3 with surface FcεRI levels unchanged, this acquisition is reversible and probably reflects intracellular events requiring protein synthesis. Interestingly, similar activation‐associated acquisition was observed for responsiveness to other stimuli, including CD200R3 CL, which is known to signal via DAP‐12, and the allergen protease papain. This acquisition of responsiveness to FcεRI CL was inhibited by Jak inhibitor. Thus, the IL‐3 signal bifurcates downstream of Jak, into two distinct pathway, one leading to IL‐4 production and the other to render basophils competent to respond to stimuli dependent on ITAM‐containing adaptors DAP12 and FcRγ for IL‐4 production.