Prof. Dr. Lars Nitschke
Lehrstuhl für Genetik
Prof. Dr. Thomas Winkler
Nikolaus-Fiebiger-Zentrum für Molekulare Medizin
Transgenic mouse unit/ B-VARIA mice
Genetically modified mice are crucial model systems for B-cell immunology. Both transgenic mice with defined BCRs, as well as conventional knockout mice or mice with conditional alleles that allow tissue-specific and inducible deletion of genes have been very valuable in all aspects of B-cell immunology. This central unit will provide transgenic / gene knockout technology for the whole consortium. An existing central transgenic facility at the Franz-Pentzold centre (FPZ) at the University of Erlangen will be supported by this central unit of the Transregio-SFB. This central unit will improve existing protocols and will further develop new techniques. Open questions in B-cell development are central and peripheral selection checkpoints and lineage decisions within the B-cell maturation processes. To obtain information about clonal relationships of B-lymphocytes during the development of B-cell lineages, immune responses and particularly during the germinal centre response, the central unit plans to develop a transgenic B-cell marker system where individual B-cell clones are marked in vivo by specific fluorescent markers. B cell specific expression will be achieved by a CD19 promoter expression cassette and three to four loxP-flanked fluorescent proteins, which will be induced with a stochastic choice of different fluorescent combinations and different expression levels by B-cell specific Cre or inducible Cre-mice. After successful establishment of these novel mouse strains they will be used for several scientific questions in different projects within this consortium.
Krzyzak, L., Seitz, C., Urbat, A., Hutzler, S., Ostalecki, C., Glasner, J., Hiergeist, A., Gessner, A., Winkler, T.H., Steinkasserer, A., and Nitschke, L. (2016). CD83 Modulates B Cell Activation and Germinal Center Responses. J Immunol 196, 3581-3594.
Ozgor, L., Brandl, C., Shock, A., and Nitschke, L. (2016). Epratuzumab modulates B-cell signaling without affecting B-cell numbers or B-cell functions in a mouse model with humanized CD22. Eur J Immunol 46, 2260-2272.
Hutzler, S., Ozgor, L., Naito-Matsui, Y., Klasener, K., Winkler, T.H., Reth, M., and Nitschke, L. (2014). The ligand-binding domain of Siglec-G is crucial for its selective inhibitory function on B1 cells. J Immunol 192, 5406-5414.
Brachs, S., Turqueti-Neves, A., Stein, M., Reimer, D., Brachvogel, B., Bosl, M., Winkler, T., Voehringer, D., Jack, H.M., and Mielenz, D. (2014). Swiprosin-1/EFhd2 limits germinal center responses and humoral type 2 immunity. Eur J Immunol 44, 3206-19.