First Author | Savignac M | Year | 2010 |
Journal | J Immunol | Volume | 185 |
Issue | 12 | Pages | 7527-36 |
PubMed ID | 21059893 | Mgi Jnum | J:167478 |
Mgi Id | MGI:4868332 | Doi | 10.4049/jimmunol.1000152 |
Citation | Savignac M, et al. (2010) Increased B cell proliferation and reduced Ig production in DREAM transgenic mice. J Immunol 185(12):7527-36 |
abstractText | DREAM/KChIP-3 is a calcium-dependent transcriptional repressor highly expressed in immune cells. Transgenic mice expressing a dominant active DREAM mutant show reduced serum Ig levels. In vitro assays show that reduced Ig secretion is an intrinsic defect of transgenic B cells that occurs without impairment in plasma cell differentiation, class switch recombination, or Ig transcription. Surprisingly, transgenic B cells show an accelerated entry in cell division. Transcriptomic analysis of transgenic B cells revealed that hyperproliferative B cell response could be correlated with a reduced expression of Klf9, a cell-cycle regulator. Pulse-chase experiments demonstrated that the defect in Ig production is associated with reduced translation rather than with increased protein degradation. Importantly, transgenic B cells showed reduced expression of the Eif4g3 gene, which encodes a protein related to protein translation. Our results disclose, to our knowledge, a novel function of DREAM in proliferation and Ig synthesis in B lymphocytes. |