TY - JOUR
T1 - Reconstitution of a functional human type II IL-4/IL-13 receptor in mouse B cells
T2 - Demonstration of species specificity
AU - Andrews, R. P.
AU - Rosa, L. R.
AU - Daines, M. O.
AU - Khurana Hershey, G. K.
PY - 2001/2/1
Y1 - 2001/2/1
N2 - 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 α-chain, IL-4Rα, and at least two other cell surface proteins, IL-13Rα1 and IL-13Rα2, which specifically bind IL-13. IL-13 has been reported to have very limited effects on mouse B cells. It was unclear whether this was due to a lack of receptor expression, a disproportionate relative expression of the receptor components, or an additional subunit requirement in B cells. To determine the requirements for IL-13 signaling in murine B cells, we examined IL-13-dependent 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 unresponsive to IL-13, and did not express IL-13 receptor. B220+ splenocytes also failed to signal in response to IL-13 and did not express IL-13 receptor. We transfected A201.1 cells with human IL-4Rα, IL-13Rα1, or both. Transfectants expressing either human IL-4Rα or human IL-13Rα1 alone were unable to respond or signal to IL-13. Thus, human IL-13Rα1 could not combine with the endogenous murine IL-4Rα to generate a functional IL-13R. However, cells transfected with both human IL-4Rα and IL-13Rα1 responded to IL-13. Thus, the relative lack of IL-13 responsiveness in murine B cells is due to a lack of receptor expression. Furthermore, the heterodimeric interaction between IL-4Rα and IL-13Rα1 is species specific.
AB - 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 α-chain, IL-4Rα, and at least two other cell surface proteins, IL-13Rα1 and IL-13Rα2, which specifically bind IL-13. IL-13 has been reported to have very limited effects on mouse B cells. It was unclear whether this was due to a lack of receptor expression, a disproportionate relative expression of the receptor components, or an additional subunit requirement in B cells. To determine the requirements for IL-13 signaling in murine B cells, we examined IL-13-dependent 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 unresponsive to IL-13, and did not express IL-13 receptor. B220+ splenocytes also failed to signal in response to IL-13 and did not express IL-13 receptor. We transfected A201.1 cells with human IL-4Rα, IL-13Rα1, or both. Transfectants expressing either human IL-4Rα or human IL-13Rα1 alone were unable to respond or signal to IL-13. Thus, human IL-13Rα1 could not combine with the endogenous murine IL-4Rα to generate a functional IL-13R. However, cells transfected with both human IL-4Rα and IL-13Rα1 responded to IL-13. Thus, the relative lack of IL-13 responsiveness in murine B cells is due to a lack of receptor expression. Furthermore, the heterodimeric interaction between IL-4Rα and IL-13Rα1 is species specific.
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U2 - 10.4049/jimmunol.166.3.1716
DO - 10.4049/jimmunol.166.3.1716
M3 - Article
C2 - 11160216
AN - SCOPUS:0035253495
SN - 0022-1767
VL - 166
SP - 1716
EP - 1722
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -