Telomerase activation in normal B lymphocytes and non-Hodgkin's lymphomas

Abstract

Activation of telomerase seems to be a prerequisite for immortalization and is found in permanent cell lines and most malignant tumors. Normal somatic cells are generally telomerase negative, except for bone marrow stem cells. Weak activity is also present in peripheral blood cells. In the present study strong telomerase activity was demonstrated in vivo in normal mature cells of the immune system, as well as in malignant lymphomas. Benign lymph nodes had lower telomerase activity than benign tonsils, which exhibited intermediate to high activity comparable with findings in malignant lymphomas. In benign tonsils the activity seemed to be restricted to germinal center B cells. In benign lymphoid tissues telomerase activity correlated with B-cell numbers and cell proliferation, but this was not observed in the lymphoma group. High- grade lymphomas exhibited higher levels of telomerase compared with low- grade cases. The data showed that in vivo activation of telomerase is a characteristic feature of germinal center B cells. Different signals for activation of telomerase are likely to exist, one of them being immune stimulation. The data suggest that telomerase activity in malignant lymphomas can be explained by an “induction and retention” model, ie, transformation occurs in a normal, mature B cell with reactivated telomerase, which is retained in the neoplastic clone.

Exogenous TERC alone can enhance proliferative potential, telomerase activity and telomere length in lymphocytes from dyskeratosis congenita patients

“…With fibroblast studies, the results were reliant upon exogenous TERT because fibroblasts do not express it endogenously. T and B lymphocytes however, typically do express telomerase (Broccoli et al, 1995;Norrback et al, 1996) and we showed that telomere length maintenance was improved in the B-LCLs studied here in the presence only of endogenous TERT. That telomerase activity can be increased with TERC alone suggests that lymphocytes express an excess of TERT, above the level that the available TERC pool can sustain for maximal enzymatic activity.…”

Telomere/telomerase interplay in virus‐driven and virus‐independent lymphomagenesis: pathogenic and clinical implications

“…Similarly to T cells, quiescent circulating B lymphocytes express low to undetectable levels of telomerase. 65 Nevertheless, peripheral blood B cells show peculiar telomere dynamics, distinctly different from other blood cell populations. In fact, when compared to T cells, natural killer cells, and monocytes, B lymphocytes have notably longer telomeres and higher telomerase activity.…”

“…[77][78][79][80] During a classical T cell-mediated GC experience, normal B cells have high levels of telomerase and exhibit telomere lengthening. 65,67 Within this context, studies on B cell chronic lymphocytic leukemia (B-CLL) are of particular interest. B-CLL is the most common leukemia in adults and is clinically highly heterogeneous.…”

Telomerase Enzyme Activity as a Diagnostic Tool to Distinguish Effusions of Malignant and Benign Origin

“…Reports have documented the presence of telomerase in activated lymphocytes. [24][25][26][27] For this reason, detection of telomerase activity may also be an inconclusive finding in the setting of substantial inflammation. In the present study, telomerase activity was detected in 2 effusions with a significant inflammatory cell population, and was absent in 6 others having a similar cell population based on microscopic evaluation.…”