Reconstitution of a functional human type II IL-4/IL-13 receptor in mouse B cells: 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-4Ralpha, and at least two other cell surface proteins, IL-13Ralpha1 and IL-13Ralpha2, 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-4Ralpha, IL-13Ralpha1, or both. Transfectants expressing either human IL-4Ralpha or human IL-13Ralpha1 alone were unable to respond or signal to IL-13. Thus, human IL-13Ralpha1 could not combine with the endogenous murine IL-4Ralpha to generate a functional IL-13R. However, cells transfected with both human IL-4Ralpha and IL-13Ralpha1 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-4Ralpha and IL-13Ralpha1 is species specific.
Andrews
R
R
Division of Pulmonary Medicine, Allergy, and Clinical Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Rosa
L
L
Daines
M
M
Khurana Hershey
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D018793:Interleukin-13 / Q000378:metabolism / Q000502:physiology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D017493:Leukocyte Common Antigens