Wed, 2013-04-17 12:17 | 
Members of the tumor necrosis factor superfamily of ligands and their receptors are critical regulators of the adaptive immune system. Dysregulated signaling by TNFRSF members can promote survival and proliferation causing autoimmunity and neoplasia (i). TNFRSF13B is encoding the protein TACI and TNFRSF13C is encoding the protein BAFFR. TNFRSF13B is expressed on B cells and a subset of activated T cells and the function of this protein has been elusive with TACI mutant mice revealing two sides of this receptor, a positive one driving T cell independent immune responses and a negative one down regulating B cell activation and expansion. TACI paradoxically has the ability to induce both survival and apoptotic signals. BAFF and APRIL are the ligands of TACI and these interactions lead to the: survival and differentiation of B cells, T cell independent immune responses, antiboby production, isotype switching and on the other hand in the homeostasis of B cells. TNFRSF13C is expressed on B cells and on a subset of T cells. BAFFR interacts only with BAFF and triggers the differentiation of B cells (ii). ICOS belongs to the CD28 family of costimulatory molecules and is expressed exclusively on activated T cells. It has at least three critical functions: germinal center formation, isotype class switching, and the development of memory B cells. The discovery of human ICOS deficiency showed that a monogenic disorder could account for the full spectrum of manifestations seen in childhood and adulthood-onset CVID, including autoimmune, inflammatory, and malignant disease complications, as well as recurrent infections (iii).
Malignant B cells can express TACI and BAFFR but their role in the survival and the prognosis of B-CLL patients is elusive. Recent studies have shown that TACI protects BCLL cells from apoptosis (iv,v). For this reason, anti-TACI, anti-BAFF and anti-APRIL therapeutic approaches are now available, for the treatment of patients with autoimmune diseases and might be useful in patients with B-CLL (vi).
Taking into account that for the qualitative and quantitative expression of TACI, BAFFR and ICOS, few reports have appeared, the aim of this study is the determination of TNFRSF13B/TACI TNFRSF13C/BAFFR and ICOS expression in LPDs patients and their contribution to the phenotype and the prognosis of the disease.
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