Viral Interleukin 6 Stimulates Human Peripheral Blood B Cells That Are Unresponsive to Human Interleukin 6

• Published in: Cellular immunology 2001-09, Vol.212 (2), p.118-125
• Main Authors: Breen, Elizabeth C., Gage, Julia R., Guo, Beichu, Magpantay, Larry, Narazaki, Masashi, Kishimoto, Tadamitsu, Miles, Steve, Martínez-Maza, Otoniel
• Format: Article
• Language: English
• Subjects: activation; Adult; Animals; Antigens, CD - metabolism; B cell; B-Lymphocyte Subsets - drug effects; B-Lymphocyte Subsets - immunology; CD126′IL6R; CD130 antigen; CD130′gp130; Cells, Cultured - drug effects; Cells, Cultured - immunology; Culture Media, Conditioned - pharmacology; cytokine; Cytokine Receptor gp130; DNA-Binding Proteins - metabolism; glycoprotein gp130; Herpesvirus 4, Human - physiology; Herpesvirus 8, Human - physiology; HHV-8; human; Humans; IL6; Interleukin-6 - pharmacology; Lymphocyte Activation - drug effects; Membrane Glycoproteins - metabolism; Mice; Phosphorylation - drug effects; Protein Processing, Post-Translational - drug effects; Receptors, Interleukin-6 - metabolism; Recombinant Fusion Proteins - pharmacology; Signal Transduction - drug effects; STAT3 Transcription Factor; Trans-Activators - metabolism; Transfection; vIL6; Viral Proteins - pharmacology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.2001.1852

Cellular responsiveness to human interleukin 6 (hIL6) requires the expression of two receptor molecules: IL6-specific receptor (CD126′IL6R′) and a nonspecific signal-transducing molecule (CD130′gp130′). Regulation of responsiveness to hIL6 is generally controlled by CD126′IL6R′ expression. A viral homologue of hIL6 (vIL6) is encoded by human herpesvirus-8 and has biologic activity similar to hIL6 on a number of cell lines. vIL6 differs from hIL6 in its receptor utilization, requiring only CD130′gp130′. Total human B cells isolated from peripheral blood, which are predominantly CD126′IL6R′-negative, as well as sorted CD126′IL6R′-negative B cells, could be stimulated by recombinant vIL6, but not by hIL6, as indicated by induction of IL6-like signaling (STAT3 phosphorylation). This suggests that the ability of vIL6 to stimulate B cells expressing little or no CD126′IL6R′ allows it to act on a larger pool of target B cells, compared to human IL6.