Reconstitution of a functional human type IIIL-4/IL-13 receptor in mouse Bcells: Demonstration of species specificity

IL-13 is a Th2-derived pleiotropic cytokine that recently was shown to be a key mediator of allergic asthma, IL-13 mediates its effects via a complex receptor system, which includes the IL-4R alpha -chain, IL-4R alpha, and at least two other cell surface proteins, IL-13R alpha1 and IL-13R alpha2, wh ich specifically bind IL-13, IL-13 has been reported to have very limited e ffects on mouse B cells. It was unclear whether this was due to a lack of r eceptor expression, a disproportionate relative expression of the receptor components, or an additional subunit requirement in B cells. To determine t he requirements for IL-13 signaling in murine B cells, we examined IL-13-de pendent Stat6 activation and CD23 induction in the murine B cell line, A201 .1. A201.1 cells responded to murine IL-4 via the type I IL-4R, but were un responsive to IL-13, and did not express IL-13 receptor. B220(+) splenocyte s also failed to signal in response to IL-13 and did not express IL-13 rece ptor. We transfected A201.1 cells with human IL-4R alpha, IL-13R alpha1, or both. Transfectants expressing either human IL-4R alpha or human IL-13R al pha1 alone were unable to respond or signal to IL-13, Thus, human IL-13R al pha1 could not combine with the endogenous murine IL-4R alpha to generate a functional IL-13R, However, cells transfected with both human IL-4R alpha and IL-13R alpha1 responded to IL-13, Thus, the relative lack of IL-13 resp onsiveness in murine B cells is due to a lack of receptor expression, Furth ermore, the heterodimeric interaction between IL-4R alpha and IL-13R alpha1 is species specific.