Differentiation of B-1 lymphocytes into insulin producing cells: mechanisms involved and optimization of the process

• Grant number: 17/04434-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2018
• End date: February 14, 2021
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Rui Curi
• Grantee: Anuska Marcelino Alvares Saraiva
• Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil

Abstract

The candidate (Alvares-Saraiva et al., 2015) demonstrated, for the first time, a regulatory role of B-1 lymphocytes in the control of glycemia in Type I Diabetes streptozotocin (STZ)-induced. As the main point, the adoptive transfer of B-1 lymphocytes from WT mice to XID mice (deficient in B-1 lymphocytes) has become them resistant to Diabetes induction. Also, insulin-producing cells were identified in adherent peritoneal cell cultures obtained from WT mice but not in cells derived from XID mice. When re-cultivated, B-1 lymphocytes differentiate into insulin-producing cells. Insulin granules into cell cytoplasm were identified by immunofluorescence and the presence of the insulin gene in differentiated B-1 lymphocytes were confirmed by the RT-PCR. Considering: 1) B-1 lymphocytes have characteristics of pluripotent cells; 2) it was been observed B-1 differentiation into phagocytes and osteoclasts with similar morphology and function to the corresponding cells; 3) to obtain a cell with insulin production ability, instead of pancreatic ²-cells, it may help the treatment or even cure of type I diabetic patients, it is our aim to determine the stimuli and the mechanisms involved in the differentiation of B-1 cells into insulin-producing cells. This study was divided into 3 parts to attend: 1) to compare insulin-producing B-1 cells and pancreatic ²-cells in terms of their morphological, ultrastructural and metabolic characteristics; 2) to identify insulin-producing B-1 cells in vivo, using luciferase-transduced B-1 cells adoptively transferred; 3) to induce and to optimize the generation of these cells using inflammatory stimulus in vivo and conditioned medium in vitro. (AU)