Activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) gene. AID has been reported to be specifically expressed in the germinal center (GC). Follicular lymphoma (FL) cells are known to be exposed to GC reaction, as characterized by a high degree of SHM with some heterogeneity in terms of intraclonal microheterogeneity and antigen selection. The heterogeneity of SHM pattern in FL intrigued us to investigate the AID expression. AID expression was investigated in 19 FL materials consisting of 15 cases of FL fresh cells and four cell lines. In all, 10 fresh cells and three cell lines expressed AID, but the others did not. SHM was investigated in 12 fresh cells and four cell lines. The ongoing mutation was significantly different between AID-positive and AID-negative FL fresh cells (unpaired Student's t-test, P ¼ 0.047). Ongoing mutation was not seen in any of the cell lines. AID expression was associated with the ongoing mutation in FL fresh cells (two-tailed Pearson's coefficient correlation, r ¼ 0.899, P ¼ 0.01). The switch off of AID expression may start in the B-lineage differentiation stage counterpart of FL after optimizing SHM, indicated by the cessation of the ongoing mutation in AID-negative FL fresh cells.
Activation-induced cytidine deaminase (AID) is an enzyme that catalyzes somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) gene. The expression of AID was reported to be confined to the germinal center (GC). Burkitt lymphoma (BL) cells are regarded as being derived from GC cells. BL cells have been reported to have SHM in the Ig gene with variety in terms of degree, antigen selection and ongoing mutation characteristic. We investigated the expression of AID in 15 BL cell lines by RT-PCR. In only 2 BL cell lines, Tree92 and Black93, AID expression was not detected, and the 1gVH gene of these 2 cell lines was not mutated. Tree92 expresses terminal deoxy-nucleotidyl transferase (TdT) and recombination activating gene (RAG)1, but Black93 does not, as is typical of the BL phenotype. BL cells are generally derived from GC B-cell expressing AID, but are rarely derived from the stage of B-lineage differentiation in which AID is not yet expressed, causing the absence of mutation in the IgVH.
As AID and SHM are generally regarded as properties exhibited by mature B cells, the presence of AID and SHM in this study seems to be incompatible with the general understanding of the early stage derivation of ALL in B-lineage differentiation. The results here give some insight into the relationship between disease type (ALL or lymphoma) and derivation stage, the overlapping of the early stage phenotype and the mature genomic characteristics, and the probable relationship between the mechanism of the occurrence of t(14;18)(q32;q21) and the machinery causing SHM.
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