Chronic lymphocytic leukemia B cells expressing AID display dissociation between class switch recombination and somatic hypermutation

• Published in: Blood 2003-05, Vol.101 (10), p.4029-4032
• Main Authors: Oppezzo, Pablo, Vuillier, Françoise, Vasconcelos, Yuri, Dumas, Gérard, Magnac, Christian, Payelle-Brogard, Béatrice, Pritsch, Otto, Dighiero, Guillaume
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; B-Lymphocytes - immunology; Base Sequence; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Cytidine Deaminase - blood; Cytidine Deaminase - genetics; DNA Primers; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects. Ontogeny. Phylogeny; Humans; Immunobiology; Leukemia, Lymphocytic, Chronic, B-Cell - enzymology; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Medical sciences; Mutation; Polymerase Chain Reaction; Recombination, Genetic; Reference Values; RNA Editing - immunology; Transcription, Genetic; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-10-3175

In B cells, somatic hypermutation (SHM) and class switch recombination (CSR) depend on the activation-induced cytidine deaminase (AID) gene product, although the precise mode of action of AID remains unknown. Because 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 the preswitch μ DNA region, CSR, and the SHM in 65 CLL patients. Our results demonstrate that unmutated CLL B cells can constitutively express AID and that AID expression is associated with the presence of mutations in the preswitch region and in clonally related isotype-switched transcripts. They also demonstrate that in CLL without constitutive AID expression, AID induction on stimulation results in preswitch mutations and the CSR process. Our results show a dissociation between SHM and CSR in CLL and suggest that, in this disease, AID would require additional help for carrying out the SHM process.