"Null" Phenotype of persistently KSHV-infected B-Lymphocytes

Iotzova, Guergana (2005): "Null" Phenotype of persistently KSHV-infected B-Lymphocytes. Dissertation, LMU München: Fakultät für Biologie

Abstract

Kaposi´s sarcoma-associated herpesvirus (KSHV) is involved in the pathogenesis of Kaposi´s sarcoma (KS) and some atypical B-cell lymphomas. The aim of this study was to investigate the influence of KSHV-infection on cellular gene expression in B-lymphocytes. In order to study the gene expression profile a microarray screen was performed using B-cells that have been persistently infected with KSHV in vitro. A considerable number of genes (408) were found to be modulated more than 4-fold by KSHV infection, 275 (67.4 %) were downregulated whereas 133 (32.6%) were upregulated. A multitude of the downregulated genes encoded for B-cell surface markers and several B-cell specific transcription factors (PAX-5, Oct-2 and Spi-B) which was confirmed by RT-PCR and on the protein level. The massive loss of B-cell surface markers or “null” phenotype, was similar to tumor cells isolated from primary effusion lymphoma (PEL). Thus, the loss of B-cell identity is due to KSHV-infection and not to cellular tumor-promoting events. Moreover, this study demonstrated that the “null” phenotype is caused by a soluble factor(s) released from KSHV-infected B-cells. The downregulation of B-cell markers led to severe functional defects, as KSHV-infected B-cells could not be activated by crosslinking of the B-cell receptor. Importantly, KSHV-infected cells could not be lysed by allo-reactive cytotoxic T-cells, suggesting that the “null” phenotype serves as a mechanism for immune escape.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: KSHV, PEL, Pax-5, B-cells
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Fakultät für Biologie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 1. Juli 2005
• 1. Bericht­erstatter:in: Schartau, Walter