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Different isoforms of BSAP regulate expression of AID in normal and chronic lymphocytic leukemia B cells.

Abstract : Activation-induced cytidine deaminase (AID) is key to initiating somatic hypermutation (SHM) and class switch recombination (CSR), but its mode of action and regulation remains unclear. Since Pax-5 and Id-2 transcription factors play an opposing role in AID regulation, we have studied the expression of Pax-5, Id-2, and prdm-1 genes in 54 chronic lymphocytic leukemia (CLL) B cells. In 21 cases, presence of AID is constantly associated with high expression of the complete form of the Pax-5 gene (Pax-5a) and lower expression of the Id-2 and prdm-1 transcripts. In 33 cases, the absence of AID expression and CSR is associated with a reduction of Pax-5a and the appearance of a spliced form with a deletion in exon 8 (Pax-5/Delta-Ex8). Stimulation with CD40L+interleukin 4 (IL-4) induces CSR, the presence of AID transcripts, up-regulation of Pax-5a and down-regulation of Pax-5/Delta-Ex8, and Id-2 and prdm-1 transcripts. Pax-5a and Pax-5/Delta-Ex8 are translated into 2 isoforms of the B-cell-specific activator protein (BSAP) and both are able to bind the AID-promoter region. Overall, these results suggest that Pax-5/Delta-Ex8 could play an important role in the control of its own transcription and indirectly in AID expression and CSR.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00177462
Contributor : Hélène Ribierre <>
Submitted on : Monday, October 8, 2007 - 11:24:56 AM
Last modification on : Friday, June 12, 2020 - 9:54:02 PM

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Pablo Oppezzo, Gérard Dumas, Ana Inés Lalanne, Béatrice Payelle-Brogard, Christian Magnac, et al.. Different isoforms of BSAP regulate expression of AID in normal and chronic lymphocytic leukemia B cells.. Blood, American Society of Hematology, 2005, 105 (6), pp.2495-503. ⟨10.1182/blood-2004-09-3644⟩. ⟨pasteur-00177462⟩

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