Reconsttution of a FunctionalHuman Type II IL-4/IL-13 Receptor inMouse B Cells:Demonstration of Species Specificity

摘要

IL-13 is a Th2-derived pleiotropic cytokine that recently was shown to be a key mediator of allergic asthma. IL-13 mediates its Ifects via a complex receptor system, which includes the IL-4R a-chain, IL-4Ra, and at least two other cell surface proteins, L-13Ra1 and IL-13Ra2, which specifically bind IL-13. IL-13 has been reported to have very limited effects on mouse B cells. It ras unclear whether this was due to a lack of receptor expression, a disproportionate relative expression of the receptor com- onents, or an additional subunit requirement in B cells. To determine the requirements for IL-13 signaling in murine B cells, we ~amined IL-13-dependent Stat6 activation and CD23 induction in the murine B cell line, A201.1. A201.1 cells responded to lurine IL-4 via the type I IL-4R, but were unresponsive to IL-13, and did not express IL-13 receptor. B220+ splenocytes also riled to signal in response to IL-13 and did not express IL-13 receptor. We transfected A201.1 cells with human IL-4Ra, L-13Ra1, or both. Transfectants expressing either human IL-4Ra or human IL-13Ra1 alone were unable to respond or signal ) IL-13. Thus, human IL-13Ra1 could not combine with the endogenous murine IL-4Ra to generate afunctional IL-13R. [owever, cells transfected with both human IL-4Ra and IL-13Ra1 responded to IL-13. Thus, the relative lack of IL-13 respon- lveness in murine B cells is due to a lack of receptor expression. Furthermore, the heterodimeric interaction between IL-4Ra and L-13Ra1 is species specific.