Regulatory Role of Interleukin 5 and Its Receptor in the Bcell Growth and Differentiation

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We have characterized human IL-5 receptor (hIL-5R) by cloning cDNA with cross-species hybridization using murine IL-5R alpha chain cDNA as a probe. One cDNA clone encodes a glycoprotein of 420 amino acids (Mr 47, 670) with an N-terminal hydrophobic region (20 amino acids), a glycosylated extracellular domain (324 amino acids), a transmembrane domain (21 amino acids) and a cytoplasmic domain (55 amino acids).COS7 cells transfected with the cDNA expressed a 6OkD protein and bound IL-5 with a single class of affinity (Kd : 250-590 pM). The Kd values were similar with that observed in normal human eosinophils. The hIL-5R alpha chain characterized in this paper is an essential molecule for signal transduction, because expression of this molecule in murine IL-3 dependent cell line FDC-P1 allow these cells to proliferate in response to IL-5.In contrast to murine 60 kD alpha chain that binds IL-5 with low affinity (Kd : -IO nM), human alpha chain can bind IL-5 With much higher affinity by itself. In murine system, coexpression of beta chain (AIC2B, IL-3R homologue) with alpha chain increased the affinity at least 100-fold to that of alpha chain alone. Although hIL-5R alpha chain probably makes heterodyne with human GM-CSF receptor beta chain shared with IL-3 receptor, the contribution of hIL-5R beta chain to the increase of the affinity of alpha chain seems to be marginal. This may provide us an easier way to regulate eosinophil growth in human by designing an antagonist to hIL-5R alpha chain.We have also characterized several other cDNA clones for hIL-5R alpha chain with diversified 3' end. One of which does not have the transmembrane and cytoplasmic domains and probably codes for a soluble form of IL-5R alpha chain. These diversified 3' end may be involved in the regulation of the growth and differentiation of human eosinophils.