TRAIL-R1 and TRAIL-R2 Mediate TRAIL-Dependent Apoptosis in Activated Primary Human B Lymphocytes

In conclusion, this study provides a systematic analysis of the expression of TRAIL-Rs in human primary B cells and of their capacity to signal and induce apoptosis. This dataset forms a basis to further study and understand the dysregulation of TRAIL-Rs and TRAIL expression observed in autoimmune diseases. Additionally, it will be important to foresee potential bystander immunomodulation when TRAIL-R agonists are used in cancer treatment. Introduction The homeostasis of humoral immunity requires a tight control of generation, survival, activation and maturation of B lymphocytes. Therefore, pro-survival and pro-apoptotic signals play a very important role in shaping the B cell repertoire and the long-term memory compartment. Activation-induced cell death (AICD) is a key mechanism in the control of cell expansion and selection in the germinal center (GC), where B cells are activated and change their affinity for the antigen via somatic hypermutation (1). B cells with reduced specificity or with self-reactive B cell receptors should be eliminated (2, 3). Several members of the tumor necrosis factor (TNF) receptor superfamily have been implicated in the control of B cell homeostasis. Among these, Fas (CD95, Apo-1) is involved in the control of B cell activation and GC selection (4). Mutations in Fas lead to lymphoproliferation of B and T cells, and to autoimmunity (5, 6). TNF-related apoptosis-inducing ligand receptor (TRAIL-R) 1 (aka DR4 or TNFRSF10A) and TRAIL-R2 (aka...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research