Identification and characterization of T cell subpopulations within germinal centers

• Applicant: Dr. Jakob Loschko
• Subject Area: Immunology
• Term: from 2012 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 215200570

This proposal aims to identify and characterize novel T cell subsets within the germinal center (GC) that are key for the regulation of reactions that occur within GCs (e.g. somatic hypermutation, affinity maturation). It is especially aimed to identify T cell subsets and characterize their phenotype that can be linked to either the induction or the inhibition of autoantibodies. This might eventually lead to novel therapeutic approaches that can actively manipulate GC reactions to either induce the production of antibodies (e.g. after vaccination against pathogens that have been difficult to vaccinate against) or to inhibit the occurrence of autoantibodies (e.g. in patients suffering from multiple sclerosis or lupus erythematosus).A novel transgenic mouse generated in Dr. Nussenzweig¿s laboratory expressing photoactivatable GFP will be used that allows marking anatomically defined regions. Using this technique T cells involved in an ongoing GC reaction can be marked and analyzed. Different methods will be used to either induce GC reactions and favor the occurrence of autoantibodies or to inhibit them and the presence of autoreactive antibodies to be able to investigate whether different T cell subsets are responsible for the presence or lack of autoantibodies. After suitable candidate molecules defining specific T cell subsets have been identified, their functional role can be further investigated by using either already existing knockout mice or by the generation of novel transgenic mice.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Michel C. Nussenzweig, Ph.D.