CD5 Diffuse Large B-cell Lymphoma Research Articles

CD5 + Diffuse Large B-Cell Lymphoma Consists of Germline Cases and Hypermutated Cases in the Immunoglobulin Heavy Chain Gene Variable Region

CD5+ diffuse large B-cell lymphoma (DLBCL) has recently been identified as a subgroup with different clinical characteristics from CD5- DLBCL and as having a poorer outcome than CD5- DLBCL. Data regarding differences in gene alteration between CD5+ and CD5- DLBCL have accumulated. In this article, we report an analysis of the immunoglobulin heavy-chain gene variable region (VH) gene in 35 cases of CD5+ DLBCL and compare these cases with those with the germline of the VH gene (GL-VH) and those with a somatically hypermutated VH gene (HM-VH). When the CD5+ DLBCL cases were subdivided with a cutoff value of 98% homology in the VH gene, there were 7 cases (20%) of GL-VH and 28 cases (80%) of HM-VH. The proportion of GL-VH cases in CD5+ DLBCL was more than that in CD5 DLBCL. Although we found no significant difference in pretreatment clinical parameters between the GL-VH and HM-VH subgroups, there was a tendency for the GL-VH subgroup to show lower incidences of elevation of lactate dehydrogenase and >1 site of extranodal involvement compared to the HM-VH subgroup. The overall survival curve of the HM-VH subgroup showed a rapid decline followed by a plateau, whereas that of the GL-VH subgroup declined constantly after 5 years, suggesting that GL-VH disease may not be curable by standard therapies. These findings suggest that CD5+ DLBCL with GL-VH shares clinical features with mantle cell lymphoma, the cellular origin of which has been considered to be pre-germinal center B-cells. We therefore propose that analysis of the VH gene is important for predicting the clinical course of CD5+ DLBCL.

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive and -negative diffuse large B cell lymphoma.

We analyzed nucleotide sequence and intraclonal diversity of the rearranged immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5- diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+ DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The frequencies of somatic mutation were 0.7 to 12.9% (average, 6.2%) in CD5+ DLBCL and 2.0 to 25.9% (average, 11.1%) in CD5- DLBCL. The ongoing mutation rate was estimated from the number of further single base-substitutions, expressed as a percentage of the total number of nucleotides in 10 cloned PCR products for each case (%). The averages of the ongoing mutation rate of CD5+ DLBCL (four cases) and CD5 DLBCL (seven cases) were 0.051% and 0.197%, respectively. The rate of CD5+ DLBCL was significantly lower than that of CD5- DLBCL (t-test, P = 0.024). These data may indicate that the cell origin of CD5+ DLBCL is different from that of CD5- DLBCL. CD5 is not an activated antigen in DLBCL, but a specific marker of the B1 subset of the B cells, and de novo CD5+ DLBCL may therefore be derived from this unique subset.