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.