| Abstract: |
The hematopoietically restricted member of the NF-κB/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. © 2002 Elsevier Science (USA). All rights reserved. |
| Keywords: |
controlled study; dna-binding proteins; nonhuman; animal cell; mouse; animals; mice; mice, knockout; animal tissue; cell survival; cells, cultured; cell cycle; protein bcl 2; apoptosis; gene expression; interleukin 10; neoplasm proteins; animal experiment; immunoglobulin enhancer binding protein; protein bcl xl; bcl-x protein; b lymphocyte; b-lymphocytes; mice, transgenic; cytokine; lymphocyte activation; cytokines; rna, messenger; protein mcl 1; interleukin 6; interleukin-6; stat3 transcription factor; trans-activators; proto-oncogene proteins c-bcl-2; interleukin 15; coculture techniques; stat protein; transcription factor rel; models, immunological; proto-oncogene proteins c-rel; b lymphocyte receptor; b lymphocytes; priority journal; article; c-rel knockout mice; nf-κb/rel
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