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Prepublished online as a Blood First Edition Paper on January 9, 2003; DOI 10.1182/blood-2002-10-3175.

Submitted October 21, 2002
Accepted December 23, 2002
Chronic lymphocytic leukemia B cells expressing AID display a dissociation between class switch recombination and somatic hypermutation
Pablo Oppezzo, Francoise Vuillier, Yuri Vasconcelos, Gerard Dumas, Christian Magnac, Beatrice Payelle-Brogard, Otto Pritsch, and Guillaume Dighiero*
Unite d'Immuno-hematologie, Institut Pasteur, Paris, France
Department of Hematology, Universidad Federal de Sao Paulo, Sao Paulo, SP, Brazil
Department of Biochemistry, Facultad de Medicina, Montevideo, Uruguay
* Corresponding author; email: dighiero{at}pasteur.fr.
In B-cells, somatic hypermutation (SHM) and class switch recombination (CSR) depend on the activation-induced deaminase (AID) gene product, although its precise mode of action remains unknown. Since some chronic lymphocytic leukemia (CLL) B-cells can undergo CSR without SHM, it constitutes a useful model to dissect AID function. In this work, we have studied AID expression, the presence of mutations in pre-switch µ DNA region, CSR and the SHM in 65 CLL patients. Our results demonstrate that: 1) unmutated CLL B-cells can constitutively express AID and its expression is associated to the presence of mutations in the pre-switch region and clonally related isotype-switched transcripts and 2) in CLL without constitutive AID expression, its induction upon stimulation results in pre-switch mutations and CSR process. Our results show a dissociation between SHM and CSR in CLL and suggest that, in this disease, AID would require additional help to carry out SHM process.

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