Increased B cell proliferation and reduced Ig production in DREAM transgenic mice

• Published in: The Journal of immunology (1950) Vol. 185; no. 12; pp. 7527 - 7536
• Main Authors: Savignac, Magali, Mellström, Britt, Bébin, Anne-Gaëlle, Oliveros, Juan C, Delpy, Laurent, Pinaud, Eric, Naranjo, Jose R
• Format: Journal Article
• Language: English
• Published: United States Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists 15-12-2010
• Subjects: Animals; Antibody Formation; Antibody Formation - genetics; Antibody Formation - immunology; Cell Differentiation; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Proliferation; Eukaryotic Initiation Factor-4G; Eukaryotic Initiation Factor-4G - biosynthesis; Eukaryotic Initiation Factor-4G - genetics; Eukaryotic Initiation Factor-4G - immunology; Gene Expression Regulation; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Gene Rearrangement, B-Lymphocyte; Gene Rearrangement, B-Lymphocyte - genetics; Gene Rearrangement, B-Lymphocyte - immunology; Immunoglobulins; Immunoglobulins - biosynthesis; Immunoglobulins - genetics; Immunoglobulins - immunology; Immunology; Kruppel-Like Transcription Factors; Kruppel-Like Transcription Factors - biosynthesis; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - immunology; Kv Channel-Interacting Proteins; Kv Channel-Interacting Proteins - genetics; Kv Channel-Interacting Proteins - immunology; Kv Channel-Interacting Proteins - metabolism; Life Sciences; Mice; Mice, Transgenic; Mutation; Plasma Cells; Plasma Cells - immunology; Plasma Cells - metabolism; Repressor Proteins; Repressor Proteins - genetics; Repressor Proteins - immunology; Repressor Proteins - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1000152

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.