Chronic lymphocytic leukemia B cells expressing AID display dissociation between class switch recombination and somatic hypermutation.
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 mu 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.
Oppezzo
Pablo
P
Unité d'Immuno-hématologie et d'Immunopathologie, Institut Pasteur, Paris, France.
Vuillier
Françoise
F
Vasconcelos
Yuri
Y
Dumas
Gérard
G
Magnac
Christian
C
Payelle-Brogard
Beatrice
B
Pritsch
Otto
O
Dighiero
Guillaume
G
D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000097:blood / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D016133:Polymerase Chain Reaction; D017393:RNA Editing / Q000276:immunology; D011995:Recombination, Genetic; D012016:Reference Values; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D017931:DNA Primers; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase