Role of BTK in the survival of mature B-1 cells in vitro

• Grant number: 17/04073-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2017
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Ana Flavia Popi
• Grantee: Gabriel Jun Fujishita Rodrigues
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Bruton's tyrosine kinase (BTK) is an enzyme present in B cells and its expression is very important for both development and proliferation of these cells. The engagement of an antigen in the B cell antigen receptor (BCR) triggers a signaling pathway that culminates with the activation of these lymphocytes. In this pathway, BTK phosphorylates several signaling proteins and interacts with proteins from the cytokine receptor-signaling pathway. BTK has an important role in the regulation of transcription that occurs in these cells, since it induces the activity of NFKB1, which participates in the regulation of gene expression. However, in contrast to the activation of the BCR pathway in conventional B lymphocytes, studies show that after the binding of antigens to the BCR of B-1 cells there is a decrease in the proliferative capacity of these cells and subsequently the induction of apoptosis. It's known that the absence of BCR impairs the development of B-1 lymphocytes, evidencing the role of this kinase in the precursor impairment with this cell line. Considering that the activation of BCR in B-1 cells does not induce its activation, the aim of this project is to identify if BTK is able to control the survival of mature B-1 cells, since the progenitor of these cells is not able to Develop in the absence of BTK. (AU)