Expression of activation-induced cytidine deaminase is confined to B-cell non-Hodgkin's lymphomas of germinal-center phenotype.
Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination of the immunoglobulin (IG) genes in B cells. It has recently been proposed that AID, as the newly identified DNA mutator in man, may be instrumental in initiation and progression of B-cell non-Hodgkin's lymphomas (B-NHL). We quantitatively measured, by real-time reverse-transcription PCR, expression of AID and of the error-prone DNA polymerase iota in normal B cells and a comprehensive panel of B-NHL entities. In pre- and postgerminal center (GC)-type B-NHLs like in normal naive and memory cells, AID did not exceed background levels. However, half of Burkitt lymphomas tested were found to express AID, at most at levels comparable with those found in normal GC B cells. Thirty percent of diffuse large B-cell lymphomas also transcribed AID, some at supraphysiological levels. Of follicular lymphoma cases, only 25% expressed significant amounts of AID. Moreover, within the group of GC-type B-NHLs, a statistically significant correlation between AID and polymerase iota expression was found. By contrast, we observed no correlation between AID expression and mutation load neither with the degree of intraclonal diversity of IG variable heavy chain genes. Interestingly, in two of seven follicular lymphomas with clinical and histological progression, selective outgrowth of AID-expressing clones occurred, suggestive for a role of the somatic diversification machinery in lymphoma transformation.
Smit
Laura A
LA
Department of Pathology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
Bende
Richard J
RJ
Aten
Jan
J
Guikema
Jeroen E J
JE
Aarts
Wilhelmina M
WM
van Noesel
Carel J M
CJ
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis / Q000235:genetics; D005803:Genes, Immunoglobulin / Q000235:genetics; D018858:Germinal Center / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000199:Actins; D012333:RNA, Messenger; D004259:DNA-Directed DNA Polymerase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase