Prof. Dr. Lars Nitschke

Lehrstuhl für Genetik
Department Biologie
Universität Erlangen-Nürnberg
Staudtstr. 5
91058 Erlangen 

Tel. +49 (0) 9131 85 28453
lars.nitschke@fau.de

Prof. Dr. Thomas Winkler

Lehrstuhl Genetik
Department Biologie
Nikolaus-Fiebiger-Zentrum für Molekulare Medizin
Friedrich-Alexander-Universität Erlangen-Nürnberg
Glückstr. 6
91054 Erlangen    

Tel. +49 (0) 9131 85 29136
thomas.winkler@fau.de

Project summary:

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. 

Fig. 1 Multicolour clonal labelling of B cells- principle and potential applications for B cell biology
Publications P C03:

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.