Ikaros and microRNAs in the immunosenescence of B-1 cells: a possible correlation with chronic lymphocytic leukemia

Abstract

Senescence is a normal biological process that occurs in all organisms and involve a decline in cell functions. The effects of aging on the immune system affect the production and function of B and T lymphocytes. Besides implications of immunosenescence on the susceptibility to infectious diseases, this also implicates in the increase of hyperproliferative diseases, such as autoimmune diseases and leukemias. It is known that Chronic Lymphocytic Leukemia (CLL) is more prevalent in people more than 50 years old. This disorder is result of deregulated proliferation of B-1 cells. In both human and the murine model of CLL, decreased levels of miR-15a/16 play an important role in the pathogenesis. We have recently demonstrated that Ikaros silencing, an important chromatin remodeler factor, impacts on B-1 cell proliferation and activation. Furthermore, we also demonstrated that patient LLC cells show a disruption of Ikaros expression that is probably related to induction of abnormal clonal expansion. Our purpose here is to analyze the possible role of Ikaros in regulating the expression of microRNAs, mostly miR-15a/16. We hypothesized that disruption of Ikaros complex could increase the activity of HDACs, leading to abolishment of miR-15a/16 expression and consequently deregulate proliferation and apoptosis of B-1 cells. The profile of expression of miRs by B-1 cells and B-1 cell precursors along the aging will be studied, in order to identify possible alterations that could be related to immunosenescence and the vulnerability to hyperproliferative diseases. (AU)