Idiotope-driven T-B cell collaboration is a mode of physiological immune cell regulation, which can contribute to the development of autoimmune diseases and even B cell lymphomas (Munthe et al., 2004; Munthe et al., 2007). The proposed project is an extension of the work on the “Nocturne” mouse (Huszthy et al., 2019), where we demonstrated that ligation of the B cell receptor is essential to idiotope-driven T-B-cell collaboration. In the novel mouse “Island”, a B cell receptor V-gene amino acid conversion is required before Id-driven T-B cell collaboration can start (and potentially develop into disease). The amino acid triplet conversion from F-S-N to F-R-N requires a one-codon mutation in a BCR V-gene expressed by “Island” mice. The mutation may be brought about either through antigen priming or occur spontaneously in aging mice. We have collected sera and tissue samples from mice where both these strategies have been followed.
The student will develop a quantitative PCR assay to analyze the prevalence of the relevant BCR V-gene codon mutation in splenocytes. On the protein level, the presence of the idiotope will be analyzed in splenocytes and in serum samples by Western blotting and ELISAs. The student will perform FACS staining to enumerate B cells that express the idiotope after priming experiments as well as in na?ve aging mice. Given interest, the student will also participate in priming experiments in mice.
The project will be performed at the Dept. of Immunology at OUS-Rikshospitalet with supervisors Peter Huszthy, Ramakrishna Gopalakrishnan and Ranveig Braathen.
Links:
https://www.ous-research.no/home/ous/news/20326
https://www.ous-research.no/bogen/
References:
B cell receptor ligation induces display of V-region peptides on MHC class II molecules to T cells.
Peter Csaba Huszthy, Ramakrishna Prabhu Gopalakrishnan, Johanne Tracey Jacobsen, Ole Audun Werner Haabeth, Geir ?ge L?set, Ranveig Braathen, Karl Schenck, Anders Aune Tveita, Ludvig Andre Munthe, and Bjarne Bogen. PNAS first published December 3, 2019. https://doi.org/10.1073/pnas.1902836116
Lymphomas can develop from B cells chronically helped by idiotype-specific T cells. Zangani MM, Fr?yland M, Qiu GY, Meza-Zepeda LA, Kutok JL, Thompson KM, Munthe LA, Bogen B. J Exp Med. 2007 May 14;204(5):1181-91. doi: 10.1084/jem.20061220
Systemic autoimmune disease caused by autoreactive B cells that receive chronic help from Ig V region-specific T cells. Munthe LA, Corthay A, Os A, Zangani M, Bogen B. J Immunol. 2005 Aug 15;175(4):2391-400. doi: 10.4049/jimmunol.175.4.2391