B-cell activating factor (BAFF) is the key survival factor for B-lymphocytes, yet excessive production of BAFF promotes lymphoma progression. Nevertheless, survival mechanisms activated by BAFF are only partially elucidated.
The enzyme telomerase has drawn considerable attention for its potential roles in critical biological functions, including cellular survival. Telomerase is continuously highly expressed in malignant cells, but not in normal differentiated somatic cells. This selective expression of telomerase has been determined as basis for the immortality of malignant cells. Nevertheless, recently it has been discovered that telomerase activity is also detected in normal somatic cells that have high self-renewal capacity, such as lymphocytes. The level of telomerase activity is closely regulated in the course of B-cell differentiation, and also high levels of telomerase are induced in B-cells upon activation. Up-regulation of BAFF and telomerase coexist in specific cellular environments and various clinical conditions. Consequently, this study hypothesised that BAFF cytokine may be functionally linked to telomerase regulation in lymphocytes, and that this relationship may play an essential role in immune cell homeostasis, as well as in malignancies.
It was observed that BAFF stimulation up-regulated telomerase activity in dose-dependent manner. Excess BAFF augmented telomerase activity in all B-cells subsets, yet the most affected were the marginal zone (MZ) B-cells. Moreover, it was deduced that this BAFF triggered telomerase up-regulation is driven through engaging the BAFF receptor 3 (BAFF-R), which also happens to be the same receptor engaged during B-cell survival.
The acquired data from this study strongly confirms the hypothesis that BAFF amendments telomerase activity in B-lymphocytes, and also gives an indicative of credible receptors and downstream molecular signalling pathways that might be engaged in delivering this function. This novel remark can be exploited to limit inappropriate survival of B-lymphocytes and be the basis for novel therapeutic approaches to treat B-cell lymphomas.