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Neurological B-Cell Immunology Group

The research group “Neurological B cell Immunology” is focused on the role of B cells in neuro-inflammatory diseases including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Whereas aquaporin (AQP4) autoantibodies could be clearly linked to NMOSD pathophysiology, the exact role of B cells in multiple sclerosis still remains unknown. However, B cell depleting therapies have been shown to be highly effective in multiple sclerosis indicating, that B cells play an important role in MS pathogenesis. Our primary aim is to further understand the specific functions of B cells in multiple sclerosis and other autoimmune diseases. Besides neuro-inflammatory diseases, we are also interested whether B cells are involved in the pathophysiology of primarily non-inflammatory neurological diseases (e.g. ischemic stroke and cerebral tumors) in terms of a secondary reaction after disruption of the physiological tissue architecture. 

Collaborations and partners


Immunoglobulin repertoire analysis on transcriptome level


By means of next generation mass sequencing, up to several million immunoglobulin (Ig) sequences can be assessed on transcriptome level. By using a bioinformatics approach, these Ig repertoires can be further analysed in regard to e.g. Ig subclasses, diversity and clonality. In addition, lineage analysis of clonally related B cells allows a detailed characterization of maturation and migration processes. 

Example for a B cell maturation tree with a cerebrospinal fluid B cell (blue) connecting to a peripheral blood B cell cluster (red dots). By this lineage analysis, B cell migration and maturation processes between different compartments can be studied in detail. 


Immunoglobulin repertoire analysis on proteome level


The immunoglobulin protein fraction is first separated from other proteins, digested to obtain Ig peptides and further analysed by means of mass spectrometry. The resulting Ig peptides are then aligned to the Ig transcriptome repertoires in specific regions in order to understand the dynamics of B cell maturation and actual antibody production.

Overlap between Ig transcriptome and Ig proteome: Ig peptides (marked in yellow) are aligned to Ig transcriptome sequences and checked for specificity (mutations to germline, marked in green). By this approach the dynamics between circulating B cells and actual antibody production can be characterized.    


Production of recombinant antibodies


Paired immunoglobulin heavy and light chains can by assessed by using a single cell approach in order to produce recombinant antibodies, originating from specific B cells. Those antibodies can then be tested for their specific targets and analysed in regard to functional properties.

Research Group
 Ulrike Baumann
Ulrike BaumannStudy Nurse
Neurological B-Cell-Immunology
 Deniz Bulgur
Deniz Bulgur
Neurological B-Cell-Immunology
 Evelyn Dubois
Evelyn DuboisMedical Technical Assistant
Neurological B-Cell-Immunology
07071 29-85171 
 Debbie Greis
Debbie GreisHiWi
Neurological B-Cell-Immunology
 Constanze Kemmerer
Constanze KemmererPhD Student
Neurological B-Cell-Immunology
PD Dr. Markus Kowarik
PD Dr. Markus KowarikResearch Group Leader
Neurological B-Cell-Immunology
 Aileen Lodek
Aileen LodekHIWI
Neurological B-Cell-Immunology
 Laura Neumann
Laura NeumannHIWI / Master Student
Neurological B-Cell-Immunology
Dr. Christoph Ruschil
Dr. Christoph RuschilMedical Doctor
Neurological B-Cell-Immunology
07071 29 61893 
 Michael Schlotterbek
Michael SchlotterbekDoktorand
Neurological B-Cell-Immunology
 Matthias Scholl
Matthias SchollStudy Coordinator
Neurological B-Cell-Immunology

Lepennetier G, Hracsko Z, Unger M, Van Griensven M, Grummel V, Krumbholz M, Berthele A, Hemmer B, Kowarik MC. Cytokine and immune cell profiling in the cerebrospinal fluid of patients with neuro-inflammatory diseases. J Neuroinflammation. 2019, 16(1):219.

Kowarik MC, Astling D, Gasperi C, Wemlinger S, Schumann H, Dzieciatkowska Monika, Ritchie AM, Hemmer B, Owens GP, Bennett JL. CNS Aquaporin-4 specific B cells connect with multiple B cell compartments in neuromyelitis optica spectrum disorder. Ann Clin Transl Neurol. 2017, 4(6):369-380. 

Kowarik MC, Dzieciatkowska M, Wemlinger S, Ritchie AM, Hemmer B, Owens GP, Bennett JL. The cerebrospinal fluid immunoglobulin transcriptome and proteome in neuromyelitis optica reveals central nervous system-specific B cell populations. Journal of Neuroinflammation. 2015, 12:19.

Kowarik MC, Soltys J, Bennett JL.The treatment of neuromyelitis optica. Journal of neuro-ophthalmology. 2014, 34(1):70-82.

Kowarik MC, V Grummel, S Wemlinger, D Buck, M S Weber, A Berthele, B Hemmer. Immune cell subtyping in the cerebrospinal fluid of patients with neurological diseases. Journal of Neurology. 2013, 261(1):130-43. 

Kowarik MC, Cepok S, Sellner J, Grummel V, Weber MS, Korn T, Berthele A, Hemmer B. CXCL13 is the major chemokine for B cell recruitment and B cell response in the CSF during neuroinflammation. Journal of Neuroinflammation. 2012, 9:93.

Kowarik MC, Einhäuser J, Jochim J, et al. Impact of the COMT Val108/158Met polymorphism on the mu-opioid receptor system in the human brain: mu-opioid receptor, met-enkephalin and beta-endorphin expression. Neuroscience letters. 2012, 506(2):214-9. 

Kowarik MC, Pellkofer HL, Cepok S, Korn T, Kümpfel T, Buck D, Hohlfeld R, Berthele A, Hemmer B. Differential effects of fingolimod (FTY720) therapy on immune cells in the cerebrospinal fluid and blood of multiple sclerosis patients. Neurology. 2011, 76(14):1214-21.

Kowarik M, Onofri C, Colaco T, Stalla GK, Renner U. Platelet-derived growth factor (PDGF) and PDGF receptor expression and function in folliculostellate pituitary cells. Exp Clin Endocrinol Diabetes. 2009, 118(2):113-20.

Close cooperation with PD Dr. M. Krumbholz and staff.

Prof. U. Naumann, Molecular Neurooncology, Hertie Institut für klinische Hirnforschung

Dr. S. Nahnsen, Zentrum für Quantitative Biologie (QBiC)

Dr. S. Autenrieth: Flow Cytometry Core Facility, Universitätsklinikum Tübingen

Dr. N. Casadei: Sequencing Core facility, Universitätsklinikum Tübingen


International collaborations:

Jeffrey Bennett und Greg Owens, Department of Neurology, University of Colorado, USA 


Junior research group leader
Junior research group leader
PD Dr. Markus Kowarikmarkus.kowarik@med.uni-tuebingen.deAddress

Center of Neurology
Hertie Institute for Clinical Brain Research
Department Neurology and Stroke

Hoppe-Seyler-Straße 3
72076 Tübingen

Phone: +49 (0)7071 29-68298
Fax: +49 (0)7071 29-25155