Investigation of the function and characterization of B cells associated with thermogenic adipose tissues.

• Grant number: 24/18650-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Luiz Osório Silveira Leiria
• Grantee: Anna Beatriz Costa da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Adaptive thermogenesis is the production of heat stimulated by cold or diet, this process is mediated by both the brown adipose tissue (BAT) and beige adipose tissue. Thermogenic adipose tissues are abundant in immune cells, which modulate the differentiation and activation of these tissues. B cells are central components in the assembly of the humoral immune response, and additionally, they also present other homeostatic functions, such as the regulation of systemic metabolism when present in white adipose tissue, despite the fact that the regulation of thermogenesis remains unexplored. Previous data from our research group demonstrates the presence of these cells in abundance in thermogenic adipose tissues. Furthermore, cold exposure promotes an increase in the B cell population in BAT. Therefore, we hypothesize that acute B cell depletion in adult animals positively modulates the thermogenic response. Initially, B cell subtypes will be characterized in both thermogenic adipose tissues during the chronic cold temperatures challenge through flow cytometry. Subsequently, B cells will be depleted with diphtheria toxin (DT) in adult CD19cre/wtIDTRflox/flox mice to evaluate the implications of cold sensitivity and systemic metabolism (glycemic metabolism, energy expenditure, and food intake). Additionally, BAT and beige adipose tissue will be evaluated for molecular (expression of thermogenic genes and proteins), histomorphological (lipid content and tissue characterization), and functional (high-performance respirometry) modifications. Finally, we propose the use of coculture of B cells with murine brown adipocytes (BA) to investigate the cellular communication between these cells in the modulation of BA gene expression. We hope to observe a reduction in thermogenic capacity induced by B cells associated with BAT. This project will allow our research group to continue investigating B cells in thermogenesis. Therefore, the connections between the obtained data will be of great value for understanding the function of these immune cells in the production of body temperature and regulation of the systemic metabolism.