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

Autor(es)

Souza, Olivia F. ; de Oliveira, Vivian C. ; Rodrigues, Gabriel J. F. ; Costa, Lucas V. S. ; Corado, Fernanda ; Popi, Ana F.

• Tipo de documento: Artigo Científico
• Fonte: EXPERIMENTAL HEMATOLOGY & ONCOLOGY; v. 12, n. 1, p. 6-pg., 2023-03-06.

Resumo

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. (AU)

• Processo FAPESP: 17/24451-2 - Ikaros e microRNAs na imunosenescência dos linfócitos B-1: uma possível relação com a leucemia linfocítica crônica.
• Beneficiário: Ana Flavia Popi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/27009-4 - Avaliação de microRNAs e da via de apoptose em precursores de células B-1 ao longo do envelhecimento
• Beneficiário: Olívia Fonseca Souza
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/11725-7 - Avaliação da população de precursores de células B-1 ao longo do envelhecimento: possível relação com a manifestação de doenças hiperproliferativas
• Beneficiário: Olívia Fonseca Souza
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 21/05377-1 - Alterações do perfil de miRNAs e impacto na sobrevivência de células B-1 e seus precursores durante o envelhecimento
• Beneficiário: Ana Flavia Popi
• Modalidade de apoio: Auxílio à Pesquisa - Regular