A novel mechanism for development of autoimmunity and B cell can

Problem: In the studies on this subject until now, Bogen et al. have used double transgenic mice based on a cross of an Id+ B transgenic and a TCR-transgenic strain of mice. However, the transgenic B cell part of this model suffers from certain un-physiological aspects, due to overexpression of the Id on a large proportion (~75%) of B cells. Moreover, the model has not allowed deliberate ligation of BCR, which could be crucial for B cell stimulation in addition to Id-specific T cell help.
Proposed project: With BCR knock-in technology, we have now developed a new model where mice harbor Id+ B cells and Id-specific T cells and where the B cell compartment is completely physiological. We have shown that autoimmunity develops early in these mice. Furthermore T and B cell lymphomas appear after a latency period of 10-12 months. A major part of the lymphomas have a BCR that is specific for double-stranded DNA. The project aims at sequencing BCR Ig light and heavy chains of the lymphoma tumors and thereby determine the composition of the lymphoma BCR as well as their mutational load. The projects will be performed through extensive international and national collaborations.
Significance: The results from this project may change our views on immune regulation and pathogenesis of autoimmune diseases and B cell lymphomas.
Methods needed: Common molecular biology techniques, purification of cells, culture of cells, purification of immunoglobulins, handling of mice (the successful candidate will be required to take a 1 week course), flow-cytometry, ELISA.
Supervision: The successful candidate will be supervised by Bjarne Bogen together with an experienced post doc, Peter Huszthy.
Track record, supervision of master students: Bogen has been main supervisor for 13 completed Master thesis. Successful Master students have gone on to become PhD students and postdocs. He has supervised > 40 PhD students and postdocs
Outcome of a master study: It is expected that the master project will result in a publication of high standards. This is likely since the basic aspects of the projects have already been accomplished (generation of knock-in mice that apparently have a correct BCR). Success in the project will therefore mainly depend on willingness to put in the required amount of work.
Work environment: Bogen lab is situated at Oslo University Hospital at Gaustad (Rikshospitalet). The lab is located in a relatively new building that also houses an excellent animal facility. The lab is spacy and well equipped. Access to relevant core facilities is very good. The research group consists of 23 people (senior researchers, postdocs, PhD students, master and medical students, technicians). The group is internationally flavoured (USA, England, Poland, Serbia, India, Iceland). The combined group masters a large repertoire of lab techniques necessary for execution of the project. The Bogen group is part of CoE Centre for Immune regulation and of The Jebsen Centre for Influenza Vaccine Research.