IL-6 rescues the hyporesponsiveness of c-Rel deficient B cells independent of Bcl-xL, Mcl-1, and Bcl-2

Cell Immunol. May-Jun 2002;217(1-2):47-57. doi: 10.1016/s0008-8749(02)00513-0.


The hematopoietically restricted member of the NF-kappaB/Rel family, c-Rel, is essential for B cell survival and proliferation. Here we demonstrate that the production of the interleukins 6, 10, and 15 (IL-6, IL-10, and IL-15) are diminished in c-Rel(-/-) B lymphocytes. In a manner similar to that seen in IL-6(-/-) B cells, resultant STAT activation is reduced in c-Rel(-/-) B cells following B cell receptor (BCR) ligation. Addition of either exogenous IL-6 or IL-10, but not IL-15, partially restores proliferation, and this occurs through enhanced cell survival rather than promoting cell cycle progression. This increase in viability occurs independently of Bcl-xL and Mcl-1 expression though, two survival genes reported to be downstream of IL-6 signaling. Nonetheless, transgenically expressed Bcl-xL, a direct c-Rel target gene in B cells, corrects not only the survival defect of c-Rel deficiency, but also partially ameliorates hypoproliferation. Together IL-6 and Bcl-xL are additive but incomplete in the restoration of proliferation. Known deficits in the induction of several key cell cycle components in c-Rel(-/-)B cells are not corrected upon treatment with exogenous cytokine. Together, these data demonstrate that IL-6 enhances B cell responses by employing multiple survival factors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Cell Survival
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Cytokines / pharmacology
  • DNA-Binding Proteins / metabolism
  • Interleukin-6 / pharmacology*
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Immunological
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Proto-Oncogene Proteins c-rel / genetics*
  • RNA, Messenger / biosynthesis
  • STAT3 Transcription Factor
  • Trans-Activators / metabolism
  • bcl-X Protein


  • Bcl2l1 protein, mouse
  • Cytokines
  • DNA-Binding Proteins
  • Interleukin-6
  • Mcl1 protein, mouse
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-rel
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • bcl-X Protein