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Characterization of biological and functional features of a new type of CD27- memory B lymphocytes.
Bajzíková, Martina ; Růžičková, Šárka (advisor) ; Šinkora, Marek (referee)
The increased frequencies of two novel B cell populations defined as IgM+ CD19+ CD27- CD21low CD38low CD24+ and IgM+ CD19+ CD27- CD21low CD38low CD24- in peripheral blood of patients with common variable immunodeficiency (CVID) compared to healthy donors were found. The aim was to search for such B cells in patients with rheumatoid arthritis (RA) and their further characterization. The production of immunoglobulin (Ig) mRNA in single B cells was analyzed using flow cytometry, single cell sorting and RT-PCR, IgVH-specific PCR, cycle sequencing and statistical analysis. The study was focused on analysis of variable regions of the heavy chains of Igs and significant differences in the usage of VH, DH and JH gene segments, mutational frequencies, distribution of silent and replacement mutations, length and composition of CDR3 regions, clonal relation and RAG gene expression in above mentioned B cell populations were found. Because of lack of the surface CD27 molecule being regarded as marker of B cells that have undergone antigen-driven germinal reactions, analyzed populations were considered as naive. However, the pattern and type of mutations suggested that these cells could represent a new type of differentiated memory/antigen- experienced B lymphocytes (in CVID less maturated) with the likely role in...
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Mitochondria and their role in carcinogenesis
Bajzíková, Martina ; Neužil, Jiří (advisor) ; Masařík, Michal (referee) ; Mráček, Tomáš (referee)
(EN) Mitochondria are the principal intracellular organelles responsible for fuel generation; however, they are not just cell powerhouses but are involved in a range of other intracellular functions including cell metabolism, proliferation, death, and immune responses. Loss of function in mitochondria will result in oxidative stress, which is one of the underlying causal factors for a variety of diseases including cancer. Cancer cells can predominantly produce energy by glycolysis even in the presence of oxygen. This alternative metabolic behavior is known as the "Warburg Effect." Linked to this, cancer cell mitochondria can switch between glycolysis and oxidative phosphorylation (OXPHOS) for their energy requirements and survival. The electron transport chain (ETC) function is pivotal for mitochondrial respiration, which is also needed for dihydroorotate dehydrogenase (DHODH) activity that is essential for de novo pyrimidine synthesis. In our research, we have used respiration-deficient cancer cells to challenge the dogma that mitochondria with their DNA are constrained within cells in the body. Our results document that mitochondria move from normal cells within the tumor stroma to tumor cells without mitochondrial DNA (mtDNA), resulting in long-lasting recovery of mitochondrial functions and,...
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Characterization of biological and functional features of a new type of CD27- memory B lymphocytes.
Bajzíková, Martina ; Růžičková, Šárka (advisor) ; Šinkora, Marek (referee)
The increased frequencies of two novel B cell populations defined as IgM+ CD19+ CD27- CD21low CD38low CD24+ and IgM+ CD19+ CD27- CD21low CD38low CD24- in peripheral blood of patients with common variable immunodeficiency (CVID) compared to healthy donors were found. The aim was to search for such B cells in patients with rheumatoid arthritis (RA) and their further characterization. The production of immunoglobulin (Ig) mRNA in single B cells was analyzed using flow cytometry, single cell sorting and RT-PCR, IgVH-specific PCR, cycle sequencing and statistical analysis. The study was focused on analysis of variable regions of the heavy chains of Igs and significant differences in the usage of VH, DH and JH gene segments, mutational frequencies, distribution of silent and replacement mutations, length and composition of CDR3 regions, clonal relation and RAG gene expression in above mentioned B cell populations were found. Because of lack of the surface CD27 molecule being regarded as marker of B cells that have undergone antigen-driven germinal reactions, analyzed populations were considered as naive. However, the pattern and type of mutations suggested that these cells could represent a new type of differentiated memory/antigen- experienced B lymphocytes (in CVID less maturated) with the likely role in...
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