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Kowarik Lab

Neurological B-Cell Immunology

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.

Methods
Members
Publications
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.


 
Name
Research Group
Phone
Email
 Ulrike Baumann
Ulrike BaumannStudy Nurse
B-Cell-Immunology

07071
85379

 
 Lena Beller
Lena BellerMedical Student
B-Cell-Immunology

07071
88886

 
 Deniz Bulgur
Deniz BulgurMaster Student
B-Cell-Immunology


 
 Evelyn Dubois
Evelyn DuboisTechnical Assistant
B-Cell-Immunology

07071
29-85171

 
 Celia Hinrichs
Celia HinrichsBachelor Student
B-Cell-Immunology


 
 Constanze Kemmerer
Constanze KemmererPhD Student
B-Cell-Immunology


 
 Nika Kobetic
Nika KobeticMedical Student
B-Cell-Immunology


 
PD Dr. Markus Kowarik
PD Dr. Markus KowarikResearch Group Leader
B-Cell-Immunology

07071
29-87529

 
 Annette Maier
Annette MaierTechnical Assistant
B-Cell-Immunology

+49 (0)7071-
29-88886

 
 Laura Neumann
Laura NeumannMaster Student
B-Cell-Immunology


 
 Natalie Rumpel
Natalie RumpelStudy Nurse
B-Cell-Immunology

07071
86703

 
Dr. Christoph Ruschil
Dr. Christoph RuschilPhysician
B-Cell-Immunology

07071
29 61893

 
 Michael Schlotterbek
Michael SchlotterbekPhysician
B-Cell-Immunology

+49 (0)7071-
29-85247

 
 Matthias Scholl
Matthias SchollScientific Coordinator
B-Cell-Immunology

07071
86703

 
 Nicole Vasilenko
Nicole VasilenkoPhD Student
B-Cell-Immunology

+49(0)7071/
2988886

 


Ruschil C
, Kemmerer CL, Beller L, Gabernet G, Kowarik MC. Next Generation Sequencing of Cerebrospinal Fluid B Cell Repertoires in Multiple Sclerosis and Other Neuro-Inflammatory Diseases-A Comprehensive Review. Diagnostics (Basel). 2021 Oct 11;11(10):1871.

Kemmerer CL, Schittenhelm J, Dubois E,Neumann L, Häsler LM, Lambert M, Renovanz M, Kaeser SA, Tabatabai G, Ziemann U, Naumann U, Kowarik MC. Cerebrospinal fluid cytokine levels are associated with macrophage infiltration into tumor tissues of glioma patients. BMC Cancer. 2021 Oct 15;21(1):1108.

Ruschil C, Gabernet G, Lepennetier G, Heumos S, Kaminski M, Hracsko Z, Irmler M, Beckers J, Ziemann U, Nahnsen S, Owens GP, Bennett JL, Hemmer B, Kowarik MC. Specific Induction of Double Negative B Cells During Protective and Pathogenic Immune Responses. Front Immunol. 2020 Dec 18;11:606338.

Kowarik MC, Astling D, Lepennetier G, Ritchie A, Hemmer B, Owens GP, Bennett JL. Differential Effects of Fingolimod and Natalizumab on B Cell Repertoires in Multiple Sclerosis Patients. Neurotherapeutics. 2020 Nov 30. Epub ahead of print.

Kemmerer CL, Pernpeintner V, Ruschil C, Abdelhak A, Scholl M, Ziemann U, Krumbholz M, Hemmer B, Kowarik MC. Differential effects of disease modifying drugs on peripheral blood B cell subsets: A cross sectional study in multiple sclerosis patients treated with interferon-β, glatiramer acetate, dimethyl fumarate, fingolimod or natalizumab. PLoS One. 2020 Jul 27;15(7):e0235449.

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
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