Trial Lecture - time and place
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Adjudication committee
- First opponent: Group Leader Dinis Calado, The Francis Crick Institute, London, UK
- Second opponent: Professor Therese Standal, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology
- Third member of the adjudication committee: Professor Marit Inngjerdingen, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor Erik Dissen, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo
Principal Supervisor
Associate Professor June Myklebust, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo
Summary
B lymphocytes are part of the adaptive immune system. Specific antigen encounter by binding of antigen to the B-cell antigen receptor (BCR) in naive B cells can initiate intracellular signaling and maturation into antibody-secreting plasma cells or memory B cells. In this process termed germinal centre (GC) reaction, activation of several signalling pathways will affect B-cell fate.Aberrations in different signalling pathways may influence pathogenesis of B-cell lymphoma, which are malignancies often arising from GC B cells. Aberrations can include gain of constitutive signalling in pathways promoting proliferation and survival such as the BCR signaling pathway, or alterations resulting in escape from inhibitory signalling pathways, such as bone morphogenetic proteins (BMPs).
In the thesis B-cell antigen receptor- and bone morphogenetic protein-induced signalling in normal and malignant B cells, Lise K. Bollum and colleagues aimed to investigate B-cell signalling in more detail. Using genomic editing to knock out the BCR signaling subunits CD79A and CD79B in B-cell lines, surface expression of BCR was reduced or completely lost. BCR signaling in these edited cell lines followed BCR surface expression. Characterization of mutated variants of CD79B was done by overexpressing these in cell lines or in normal memory B cells and revealed that these mutants caused a small increase in surface expression of BCR and increased maturation into plasmablasts. CD79B mutations might therefore in part account for the plasmablastic appearance of diffuse large cell B-cell lymphoma harbouring such mutations. Furthermore, while lymphoma B cells has previously been shown to be resistant to BMP-7, Bollum demonstrated that BMP-7 induced apoptosis in normal human GC B cells. A truncated variant of a TGF-β specific receptor incapable of signaling completely counteracted the effects of BMP-7, hence demonstrating greater receptor promiscuity than previously anticipated. These results have provided new insight into normal and malignant B-cell biology, which in future might help elucidating new therapeutic targets.
Additional information
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