Expression of the AID protein in normal and neoplastic B cells.
Somatic hypermutation (SHM) targets primarily the immunoglobulin variable region (IgV) genes in germinal center (GC) B cells, thereby allowing antibody affinity maturation. A malfunction of SHM, termed aberrant somatic hypermutation (ASHM), was found in about 50% of diffuse large B-cell lymphomas (DLBCLs), leading to mutations in the 5' sequences of multiple genes, including oncogenes. Although the SHM mechanism is largely unknown, it was shown to require the activation-induced cytidine deaminase (AID) gene. AID mRNA is expressed in GC B cells and GC-derived lymphomas, but the pattern of expression of the AID protein is not known. Using 2 specific antibodies, here we show that the AID protein can be detected in GC centroblasts and their transformed counterpart (Burkitt lymphoma) but not in pre-GC B cells and post-GC neoplasms, including B-cell chronic lymphocytic leukemia and multiple myeloma. DLBCLs displayed variable levels of AID expression, which did not correlate with IgV ongoing hypermutation, ASHM, or disease subtype. Finally, both in normal and malignant B cells the AID protein appeared predominantly localized in the cytoplasm. These results indicate that the AID protein is specifically expressed in normal and transformed GC B cells; nonetheless, its predominantly cytoplasmic localization suggests that additional mechanisms may regulate its function and may be altered during lymphomagenesis.
Pasqualucci
Laura
L
Institute for Cancer Genetics, Department of Pathology, Columbia University, 1150 St Nicholas Ave, New York, NY 10032, USA. lp171@columbia.edu.
Guglielmino
Roberta
R
Houldsworth
Jane
J
Mohr
Jessica
J
Aoufouchi
Said
S
Polakiewicz
Roberto
R
Chaganti
R S K
RS
Dalla-Favera
Riccardo
R
D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000502:physiology*; D002051:Burkitt Lymphoma / Q000503:physiopathology; D003564:Cytidine Deaminase; D003593:Cytoplasm / Q000201:enzymology; D043525:Cytosine Deaminase / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000503:physiopathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000503:physiopathology*; D009154:Mutation; D014066:Palatine Tonsil / Q000166:cytology; D014407:Tumor Cells, Cultured; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase