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Increased B cell proliferation and reduced Ig production in DREAM transgenic mice.
Savignac, Magali; Mellström, Britt; Bébin, Anne-Gaëlle; Oliveros, Juan C; Delpy, Laurent; Pinaud, Eric; Naranjo, Jose R.
Afiliação
  • Savignac M; Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
J Immunol ; 185(12): 7527-36, 2010 Dec 15.
Article em En | MEDLINE | ID: mdl-21059893
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.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Plasmócitos / Proteínas Repressoras / Imunoglobulinas / Rearranjo Gênico do Linfócito B / Diferenciação Celular / Proteínas Interatuantes com Canais de Kv / Formação de Anticorpos Limite: Animals Idioma: En Revista: J Immunol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Plasmócitos / Proteínas Repressoras / Imunoglobulinas / Rearranjo Gênico do Linfócito B / Diferenciação Celular / Proteínas Interatuantes com Canais de Kv / Formação de Anticorpos Limite: Animals Idioma: En Revista: J Immunol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Espanha