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

Overview

MeSH Major

  • Antineoplastic Agents
  • Interleukin-6
  • Janus Kinases
  • Neoplasms
  • STAT Transcription Factors
  • Signal Transduction

abstract

  • 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 date

  • November 28, 2002

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/S0008-8749(02)00513-0

PubMed ID

  • 12426000

Additional Document Info

start page

  • 47

end page

  • 57

volume

  • 217

number

  • 1-2