Dynamics of B cell subpopulations and immunoglobulin repertoire during experimental Plasmodium yoelii 17XNL infection

• Grant number: 24/19373-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2025
• End date: October 31, 2028
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Silvia Beatriz Boscardin
• Grantee: Nayara da Silva Antonio
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The antibody response, mediated by B lymphocytes, is crucial for controlling parasitemia and immunopathology in infection by Plasmodium, the parasite that causes malaria. B lymphocytes are divided into subpopulations based on their phenotype, anatomical location, and function. In malaria, each B lymphocyte subpopulation performs different functions and secretes antibodies with distinct specificities. However, the infection alters the composition and function of these subpopulations. Although antibodies specific to parasitic antigens are important for protective immunity against malaria, the presence of auto-reactive antibodies to erythrocyte antigens, generated during infection, has been associated with the development of autoimmune anemia. The mechanisms leading to autoimmunity during infection are not fully understood, and there is extensive debate about the role of autoantibodies in a protective or pathological response in malaria. Thus, considering the functional specificity of each B lymphocyte subpopulation and the antibodies they produce, this study aims to characterize the dynamics of B lymphocyte subpopulations and the repertoire of specific and auto-reactive antibodies after Plasmodium infection. For this, we will use the murine model of infection with the Plasmodium yoelii parasite, as it represents a good model for studying the humoral immune response and the development of anemia. The non-lethal 17XNL clone allows for the analysis of how the extent of infection can influence antibody reactivity. During the infection, blood will be collected to monitor parasitemia and the development of anemia, and serum will be analyzed for titration of antibodies specific to the parasitic MSP119 antigen and to the auto-reactive erythrocyte phosphatidylserine (PS) antigen. B lymphocyte subpopulations will be quantified at different times throughout the infection, and in parallel, the specificity of antibody-secreting cells for the targeted antigens will be evaluated in vitro. Subsequently, to characterize the contribution of each subpopulation in the production of specific and auto-reactive antibodies, the cells will be isolated and analyzed in vitro for their capacity to recognize antigens. It is expected that these analyses will improve our understanding of how B cell subpopulations cooperate in a protective or pathological response through the production of specific or auto-reactive antibodies, contributing to the development of new vaccines and immunotherapies. (AU)