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MicroRNAs and apoptosis evaluation in B-1 cells progenitors along aging

Grant number: 19/27009-4
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): June 01, 2020
Effective date (End): February 28, 2025
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Ana Flavia Popi
Grantee:Olívia Fonseca Souza
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Accumulation of mutations and changes in the immune system could happen in aging, for example, due to environmental pressures. It was seen that there is an accumulation of B-1 cells in bone marrow and lymphoid organs of old mice and our group showed that the B-1 cell progenitor (B-1p - Lin-CD45R-CD19+CD93+) population increases in the bone marrow of healthy old C57Bl/6 mice (with 30 weeks old) (Souza, O.F., not published data). Moreover, the occurrence of some diseases has a higher incidence in elderly individuals. Chronic Lymphocytic Leukemia (CLL) happens in people with more than 50th years, where there are an apoptosis failure and accumulation of B-1 cells (CD5+ B cells). Some studies in NZB/NZW[F1], the model mice to study CLL, showed that peritoneal B-1 cells can survive to irradiation and presents downregulation of miR15a/16. However, we do not know the contributions of B-1 cell progenitor to the development of CLL and there are not enough studies focusing on that. Here we pretend to elucidate the characteristics of B-1p cells and search for alterations in the apoptosis pathway in cells from old mice that could explain the hyperplasia of the population identified before and maybe maintained until the mature status of B-1 cells. These cells will be obtained from the bone marrow of these animals, enriched with cell sorting and compared with cells from young animals (with 8 weeks old). The parameters that will be evaluated are related to the occurrence and regulation of apoptosis, principally by microRNAs. We propose that the B-1 cell progenitor is involved at the beginning of the CLL and we pretend to elucidate some mechanisms involved into deregulation of apoptosis. (AU)

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