Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can induce differentiation of chronic B cell leukemia expressing the alpha subunit of IL-3 and GM-CSF receptor.
Interleukin-5 (IL-5), IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) exhibit similar functions on eosinophils, and these common functions are believed to be mediated by the shared beta chain of receptors. IL-5 shows activity on the murine chronic B cell leukemia cell line BCL1-B20, inducing differentiation into IgM-secreting cells, but IL-3 and GM-CSF do not have such activity. To elucidate whether the lineage specificity of IL-5 is due to restricted expression of the IL-5 receptor alpha chain (IL-5R alpha), transfectants of BCL1-B20 were established that express IL-3 receptor alpha (BCL1-3R) or GM-CSF receptor alpha (BCL1-GMR). BCL1-3R and BCL1-GMR acquired responsiveness to IL-3 and GM-CSF, respectively, to an extent similar to IL-5 stimulation, resulting in IgM-secreting cells. Thus, the differentiation of BCL1-B20 into IgM-secreting cells can be equally supported by either IL-3 or GM-CSF, suggesting that intracellular signaling through IL-5R can be replaced by signaling from IL-3R and GM-CSFR. These results support the notion that the lineage specificity of IL-5 is mainly due to the restricted expression of IL-5R alpha. Regulation of IL-5R alpha, IL-3R alpha and GM-CSFR alpha expression in the developmental stage appears to be important for understanding the unique function of these cytokines on a particular cell type.
Department of Immunology, Institute of Medical Science, University of Tokyo, Japan.
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Shiiba
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Takaki
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Takatsu
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D015448:Leukemia, B-Cell / Q000473:pathology*; D051379:Mice; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology*; D016185:Receptors, Interleukin-3 / Q000502:physiology*; D053649:Receptors, Interleukin-5; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D007075:Immunoglobulin M; D007377:Interleukin-3; D015848:Interleukin-5; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D053649:Receptors, Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor