Age-related accumulation of B-1 cell progenitors in mice reflects changes in miR15a/16-1 expression and radioresistance capacity

Abstract

Hyperproliferative diseases such as Chronic Lymphocytic Leukemia (CLL) and Systemic Lupus Erythematosus (SLE) are potentially related to some disturbance in the apoptosis pathway, specifically in B-1a cells (CD5+). Accumulation of B-1a cells in lymphoid organs, bone marrow or periphery is observed in some leukemia experimental murine models along aging. It is known that aging also increases the healthy B-1 cell population. However, it is not yet clear if it happens due to self-renewal of mature cells or proliferation of progenitor cells. Herein we demonstrated that the B-1 cell precursor population (B-1p) from bone marrow of middle-aged mice is higher than from young mice. Also, these aged cells are more resistant to irradiation and have downregulation of microRNA15a/16. Alterations in these microRNAs expression and in Bcl-2 regulation were already described in human hematological malignancies and new therapeutically approaches focus on that axis. This finding could explain the early events related to cell transformation during aging and correlate with beginning of symptoms in hyperproliferative diseases. Moreover, studies have already reported these pro-B-1 as a contributor to the origin of other leukemia (Acute Myeloid Leukemia - AML). Our results point to a possible relation between B-1 cell precursors and hyperproliferation during aging. We hypothesized that this population could be maintained until the mature status of the cell or reveal changes that result in re-activation of precursor in adult bone marrow, culminating in accumulation of B-1 cells later. Based on this, B-1 cell progenitor could represent an origin for B cell malignancies and a new candidate target to diagnose and treatments in the future.

Exploring the Molecular Mechanisms and Shared Gene Signatures Between Systemic Lupus Erythematosus and Bladder Urothelial Carcinoma

“…Studies have suggested that chronic myelogenous leukemia and SLE are related to disorders of apoptosis-related pathways. 58 The characteristics of malignant tumors that invade the periphery are related to the initiation of the epithelial-to-mesenchymal transition program, in which the cell adhesion function is negatively regulated. 59 Cytokines play an important role in the development of tumors and SLE.…”