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:

Steinmetz, T.D., Schlötzer-Schrehardt, U., Hearne, A., Schuh, W., Wittner, J., Schulz, S.R., Winkler, T.H., Jäck, H.-M., and Mielenz, D. (2020). TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells. Autophagy, doi: 10.1080/15548627.2020.1821546.

Weisel, F.J., Mullett, S.J., Elsner, R.A., Menk, A.V., Trivedi, N., Luo, W., Wikenheiser, D., Hawse, W.F., Chikina, M., Smita, S., Conter, L.J., Joachim, S.M., Wendell, S.G., Jurczak, M.J., Winkler, T.H., Delgoffe, G.M. and Shlomchik, M.J. (2020). GC B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis. Nat. Immunol. 21, 331–342.

Cossarizza, A., Chang, H., Radbruch, A., Acs, A., Adam, D., Adam‐Klages, S., Agace, W.W., Aghaeepour, N., Akdis, M., Allez, M., .... Winkler, T.H., et al. (2019). Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur. J. Immunol. 49, 1457–1973.

Weisenburger, T., Neubeck, B. von, Schneider, A., Ebert, N., Schreyer, D., Acs, A., and Winkler, T.H. (2018). Epistatic Interactions Between Mutations of Deoxyribonuclease 1-Like 3 and the Inhibitory Fc Gamma Receptor IIB Result in Very Early and Massive Autoantibodies Against Double-Stranded DNA. Front. Immunol. 9, 1551.

Zhang, Y., Tech, L., George, L.A., Acs, A., Durrett, R.E., Hess, H., Walker, L.S.K., Tarlinton, D.M., Fletcher, A.L., Hauser, A.E., et al. (2018). Plasma cell output from germinal centers is regulated by signals from Tfh and stromal cells. J. Exp. Medicine 215, 1227–1243.

Gruber, S., Hendrikx, T., Tsiantoulas, D., Ozsvar-Kozma, M., Goderle, L., Mallat, Z., Witztum, J.L., Rakhymzhan, A., Leben, R., Zimmermann, H., Günther, R., Mex, P., Reismann, D., Ulbricht, C., Acs, A., Brandt, A.U., Lindquist, R.L., et al. (2017). Synergistic Strategy for Multicolor Two-photon Microscopy: Application to the Analysis of Germinal Center Reactions In Vivo. Sci. Rep-UK. 7, 7101.

Sverdlov, R., Nitschke, L., and Binder, C.J. (2016). Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells. Cell Rep. 14, 2348-2361.

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.

Müller, J., Lunz, B., Schwab, I., Acs, A., Nimmerjahn, F., Daniel, C., and Nitschke, L. (2015). Siglec-G deficiency leads to autoimmunity in aging C57BL/6 mice. J. Immunol. 195, 51-60.