Browsing by Author "Quiroga Sanzana, Romina Andrea"

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    Análisis del efecto de las quimioquinas CXCL9 y CXCL10 sobre la diferenciación in vitro de linfocitos B a células plasmáticas.
    (Universidad de Concepción, 2023) Quiroga Sanzana, Romina Andrea; Nova Lamperti, Estefanía Andrea; Colombo Flores, Alicia
    Current investigations about antibody production during SARS-CoV-2 infection has revealed variations in IgG levels depending on severity. In Chilean patients, high levels of IgG antibodies against SARS-CoV-2 were observed in those who experienced a severe form of the disease, characterized by severe acute respiratory distress syndrome and the presence of lung sequelae following COVID-19 infection. Additionally, cytokines and chemokines have been found to play a significant role in the infection. Specifically, CXCL9 and CXCL10 are elevated in severe patients, a phenomenon known as the "cytokine storm." Preliminary data suggests a positive correlation between circulating levels of CXCL9 and CXCL10 and IgG antibodies against SARS-CoV-2. However, it remains unclear whether these chemokines may contribute to the exacerbation of the antibody response observed in these patients. CXCL9 and CXCL10 have also been detected in various other inflammatory diseases, and their receptor (CXCR3) have been shown to be expressed in B cells and CD4+ T helper cells involved in T cell-dependent antibody responses. The general aim of this project was to analyze the in vitro effect of CXCL9 and CXCL10 chemokines on the humoral immune response in B and T helper lymphocytes from healthy individuals. A three-phase culture system optimized for in vitro B cell differentiation was implemented and evaluated in the absence and presence of CXCL9 or CXCL10. In vitro activation of T helper lymphocytes was also assessed. Phenotypic changes in both cell populations were analyzed using flow cytometry, while the production of total IgG antibodies was assessed at the end of the protocol using ELISA. B cell activation was confirmed by the upregulation of CD86 and CD25, and the differentiation of plasma cells was confirmed by the presence of CD38hiCD27hi, and CD138+ cells. The expression of CXCR3 was also upregulated with the activation cocktail used in phase 1 and remained consistent during phases 2 and 3. Regarding CD86 expression, only CXCL9 increased its expression, whereas the presence of CXCL9 and CXCL10 significantly increased the percentage of CD38hiCD27hi cells, CD138+ cells, and IgG secretion. Finally, in the context of B cell class switch induction, it was observed that CXCL9 also increased CD40L expression in CD4+ T cells. In summary, this study demonstrated that CXCL9 and CXCL10 may play a crucial role in modulating the humoral response. In the future, it would be interesting to determine the signaling pathways through which these chemokines produce this effect.
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