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 Blood, 15 March 2005, Vol. 105, No. 6, pp. 2495-2503.
Prepublished online as a Blood First Edition Paper on November 23, 2004; DOI 10.1182/blood-2004-09-3644.

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Submitted September 21, 2004
Accepted November 17, 2004

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

Pablo Oppezzo*, Gerard Dumas, Ana I Lalanne, Beatrice Payelle-Brogard, Christian Magnac, Otto Pritsch, Guillaume Dighiero, and Francoise Vuillier

Unite d'Immuno-hematologie et d'Immunopathologie, Institut Pasteur, Paris, France
Departamento de Bioquimica, Facultad de Medicina de Montevideo, Montevideo, Uruguay

* Corresponding author; email: poppezzo{at}pasteur.fr.

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 plays an opposed role in AID regulation, we have studied the expression of Pax-5, Id-2 and prdm-1 genes, in 54 chronic lymphocytic leukaemia (CLL) B-cells. Our results show that: 1) in 21 cases, presence of AID is constantly associated with high expression of the complete form of Pax-5 gene (Pax-5a) and lower expression of Id-2 and prdm-1 transcripts. 2) in 33 cases, the absence of AID expression and CSR is associated to a reduction of Pax-5a and the appearance of a spliced form with a deletion in exon 8 (Pax-5/{Delta}-Ex8). 3) stimulation with CD40L+IL4 induces CSR, presence of AID transcripts, up-regulation of Pax-5a and down-regulation of Pax-5/{Delta}-Ex8, Id-2 and prdm-1 transcripts. 4) Pax-5a and Pax-5/{Delta}-Ex8 are translated into two isoforms of the B-cell specific activator protein (BSAP) and are both 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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G. A. Robichaud, J.-P. Perreault, and R. J. Ouellette
Development of an isoform-specific gene suppression system: the study of the human Pax-5B transcriptional element
Nucleic Acids Res., August 1, 2008; 36(14): 4609 - 4620.
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