Interleukin-1 (IL-1) receptors on murine splenic B cells and the 70Z/3 pre-B-cell line appear to be identical and bind human IL-1 alpha and IL-1 beta differentially.
In this study murine splenocytes were found to possess specific, high-affinity IL-1 receptors (IL-1R) capable of binding radiolabeled human IL-1 alpha with a Kd of 2-6 x 10(-10) M. Experiments performed with purified splenic B cells demonstrated that B cells express low levels of IL-1R (100-200 receptors per cell). Separation of splenic B cells into high- (resting) and low-density (in vivo-activated) fractions showed that low-density B cells expressed 2-fold more IL-1R compared with high-density B cells suggesting that IL-1R are upregulated on B-cell activation. In vitro stimulation of B cells with mitogens resulted in a 5- to 10-fold increase in IL-1R expression compared to IL-1R levels on unstimulated B cells. Receptors on the murine pre-B-cell line 70Z/3, which possesses type II IL-1R, and murine splenic B cells appear to be identical. Cross-linking studies demonstrated that the 125I-labeled IL-1/IL-1R complex on B cells and 70Z/3 IL-1R was found to block binding of IL-1 to IL-1R on 70Z/3 and splenic B cells, but not to type I IL-1R on murine EL4 thymoma cells. Competitive inhibition experiments showed differential binding of human IL-1 beta to splenic B cells and 70Z/3 cells as a function of temperature. The IL-1R on 70Z/3 and splenic B cells bound human IL-1 alpha, murine IL-1 alpha, and murine IL-1 beta with high affinity at both 4 degrees and 37 degrees C. In contrast, the affinity of IL-1R on these same cell types for human IL-1 beta was significantly reduced at 37 degrees C compared to 4 degrees C. The reduced binding affinity for human IL-1 beta was due to an increased off-rate at 37 degrees C compared with 4 degrees C. Characterization of IL-1R on murine splenic B cells will help clarify the role of IL-1 in the regulation of the immune response.
Powers
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Department of Immunopharmacology, Hoffmann-LaRoche, Inc., Nutley, NJ 07011.
Varnell
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Kaffka
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Chizzonite
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Kilian
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D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D001667:Binding, Competitive; D002460:Cell Line / Q000737:chemistry / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000187:drug effects; D051379:Mice; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism; D017472:Receptors, Interleukin-1; D013154:Spleen / Q000166:cytology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1