CD5 Binds to Interleukin-6 and Induces a Feed-Forward Loop with the Transcription Factor STAT3 in B Cells to Promote Cancer

Immunity. 2016 Apr 19;44(4):913-923. doi: 10.1016/j.immuni.2016.04.003.


The participation of a specific subset of B cells and how they are regulated in cancer is unclear. Here, we demonstrate that the proportion of CD5(+) relative to interleukin-6 receptor α (IL-6Rα)-expressing B cells was greatly increased in tumors. CD5(+) B cells responded to IL-6 in the absence of IL-6Rα. IL-6 directly bound to CD5, leading to activation of the transcription factor STAT3 via gp130 and its downstream kinase JAK2. STAT3 upregulated CD5 expression, thereby forming a feed-forward loop in the B cells. In mouse tumor models, CD5(+) but not CD5(-) B cells promoted tumor growth. CD5(+) B cells also showed activation of STAT3 in multiple types of human tumor tissues. Thus, our findings demonstrate a critical role of CD5(+) B cells in promoting cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • CD5 Antigens / biosynthesis
  • CD5 Antigens / metabolism*
  • Cell Line, Tumor
  • Cytokine Receptor gp130 / metabolism
  • Humans
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Janus Kinase 2 / metabolism
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NIH 3T3 Cells
  • Protein Binding
  • Receptors, Interleukin-6 / biosynthesis
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / immunology
  • STAT3 Transcription Factor / immunology*
  • Transcriptional Activation / immunology


  • CD5 Antigens
  • Cd5 protein, mouse
  • Il6st protein, mouse
  • Interleukin-6
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • interleukin-6 receptor alpha
  • Cytokine Receptor gp130
  • Jak2 protein, mouse
  • Janus Kinase 2