Reconstitution of a functional human type II IL-4/IL-13 receptor in mouse B cells: Demonstration of species specificity

R. P. Andrews, L. R. Rosa, M. O. Daines, G. K. Khurana Hershey

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1716-1722
Number of pages7
JournalJournal of Immunology
Volume166
Issue number3
DOIs
StatePublished - Feb 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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