Increased B cell proliferation and reduced Ig production in DREAM transgenic mice.
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.
Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Magali
M
Savignac
Britt
B
Mellström
Anne-Gaëlle
AG
Bébin
Juan C
JC
Oliveros
Laurent
L
Delpy
Eric
E
Pinaud
Jose R
JR
Naranjo
D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D039603:Eukaryotic Initiation Factor-4G / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
C496756:Csen protein, mouse; C549615:Eif4g3 protein, mouse; D039603:Eukaryotic Initiation Factor-4G; D007136:Immunoglobulins; C489675:Klf9 protein, mouse; D051741:Kruppel-Like Transcription Factors; D051605:Kv Channel-Interacting Proteins; D012097:Repressor Proteins