Viral interleukin 6 stimulates human peripheral blood B cells that are unresponsive to human interleukin 6.
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.
Breen
E C
EC
Department of Obstetrics and Gynecology, School of Medicine, University of California, Los Angeles, California 90095, USA. ebreen@ucla.edu
Gage
J R
JR
Guo
B
B
Magpantay
L
L
Narazaki
M
M
Kishimoto
T
T
Miles
S
S
Martínez-Maza
O
O
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D014764:Viral Proteins / Q000494:pharmacology*
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014764:Viral Proteins; D050822:Cytokine Receptor gp130