B Lenfoma Hücrelerinde Kostimülasyon ve Koinhibisyon Kapasitesinin Modülasyonu
Özet
B cells recognize antigens, produce specific antibodies, and can activate other components of the immune system. During the development and activation of B cells, they are prone to malignant transformation due to DNA breaks and mutations occurring in gene regulation and germinal center reactions. Over expression of Myc has been detected in 20% of cancer cases. It has been found that the disregularity of c-Myc affects many biological events and plays a role in lymphomagenesis. Additionally, it has been discovered that the expressions of Myc and IL-10 support each other through a positive feedback loop. BJAB is a Burkitt lymphoma cell line that possesses c-Myc amplification and is Epstein-Barr Virus (EBV) negative. However, in many studies, BJAB has been used as a B cell model. In this in vitro thesis study, the immune characterization of BJAB was determined, and by stimulating B cells with inflammatory stimuli such as IFN-γ, CD40L, and LPS, the differences in the expression of costimulatory and coinhibitory molecules were investigated, as well as the potential of BJAB to serve as a regulatory B cell model by increasing IL-10 cytokine release. Although some changes were detected in the expression of surface molecules of BJAB cells, no differences were found in the expression of coinhibitory molecules. It was found that IL-10 cytokine secretion increased under LPS condition. Additionally, while the STAT1 and STAT3 pathways were altered under long-term and short-term stimuli, it was observed that under prolonged stimulation with IFN-γ, the STAT1 pathway was dramatically affected. As a result, the immunophenotype of BJAB cells was determined, and it was considered that the effect of c-Myc amplification might be significant under inflammatory stimuli. It was concluded that in the case of c-Myc gene deletion, BJAB cells could be utilized as a regulatory B cell model.