A5030577896- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Vasculitis and related conditions
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Virology and Viral Diseases
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Bone Metabolism and Diseases
- Digestive system and related health
- COVID-19 Clinical Research Studies
- Animal Genetics and Reproduction
- Systemic Lupus Erythematosus Research
- Eosinophilic Disorders and Syndromes
- Bone health and treatments
- Immune responses and vaccinations
- Cell death mechanisms and regulation
- CAR-T cell therapy research
- Pancreatic function and diabetes
- Urticaria and Related Conditions
- Engine and Fuel Emissions
University Medical Center Freiburg
2016-2024
University of Freiburg
2015-2024
Center for Rheumatology
2018-2020
Max Planck Institute of Immunobiology and Epigenetics
2015
Max Planck Society
2015
Uniwersytecki Szpital Kliniczny w Olsztynie
1983
National Veterinary Research Institute
1968
SARS-CoV-2 spike mRNA vaccines
Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits T-cell activation and is expressed on T-regulatory cells. Human CTLA-4 deficiency results in severe immune dysregulation. Abatacept (CTLA-4 Ig) approved for the treatment of rheumatoid arthritis (RA) its mechanism action attributed to effects T-cells. It known that modulates expression ligands CD80 CD86 antigen presenting cells (APC) by transendocytosis. As B-cells express CD80/CD86 function as APC, we hypothesize are a direct target...
Although absence of interleukin-7 (IL-7) signaling completely abrogates T and B lymphopoiesis in mice, patients with severe combined immunodeficiency caused by mutations the IL-7 receptor α chain (IL-7Rα) still generate peripheral blood cells. Consequently, human has been thought to be independent signaling. Using flow cytometric analysis single-cell RNA sequencing bone marrow samples from healthy controls who are IL-7Rα deficient, combination vitro modeling B-cell differentiation, we...
Defective FAS (CD95/Apo-1/TNFRSF6) signaling causes autoimmune lymphoproliferative syndrome (ALPS). Hypergammaglobulinemia is a common feature in ALPS with mutations (ALPS-FAS), but paradoxically, fewer conventional memory cells differentiate from FAS-expressing germinal center (GC) B cells. Resistance to FAS-induced apoptosis does not explain this phenotype. We tested the hypothesis that defective non-apoptotic may contribute impaired cell differentiation ALPS. analyzed secondary lymphoid...
In the bone marrow, B cells and bone-resorbing osteoclasts colocalize form a specific microenvironment. How functionally influence architecture is poorly understood. Using genetically modified mice high-throughput analyses, we demonstrate that prolonged HIF-1α signaling in leads to enhanced RANKL production osteoclast formation. addition, deletion of prevents estrogen deficiency-induced loss mice. Mechanistically, controls protein stabilization through HSP70-mediated degradation marrow...
B-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral development to identify the causes for defect reconstitution RTX therapy.
The COVID-19 course and immunity differ in children adults. We analyzed immune response dynamics 28 families up to 12 months after mild or asymptomatic infection. Unlike adults, the initial is plasmablast-driven children. Four infection, show an enhanced specific antibody lower but detectable spike 1 protein (S1)-specific B T cell responses than their parents. While antibodies decline, neutralizing activity breadth increase both groups. frequencies of S1-specific remain stable. However,...
Background Janus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic are in clinical trials numerous other IMIDs. However, detailed studies investigating effects different JAK on B cells missing. Within this study, we therefore aimed to characterize effect inhibition cell compartment. Methods To end, investigated compartment under compared specific tofacitinib (pan-JAK), baricitinib...
The maintenance of B cell homeostasis requires a tight control generation, survival, activation, and maturation. In lymphocytes upon increased sensitivity to apoptotic signals helps controlling differentiation proliferation. death receptor Fas is important in this context because genetic mutations humans lead an autoimmune lymphoproliferative syndrome that similar lymphoproliferation observed Fas-deficient mice. contrast, the physiological role TNF-related apoptosis-inducing ligand receptors...
Detailed knowledge of human B-cell development is crucial for the proper interpretation inborn errors immunity and malignant diseases. It interest to understand kinetics protein expression changes during development, but also properly interpret major possibly alternative developmental trajectories. We have investigated samples from healthy individuals with aim describing all validated a 30-parameter mass cytometry panel demonstrated utility "vaevictis" visualization stages. used trajectory...
B cell antigen receptor (BCR) signaling is critical for development and activation. Using mass spectrometry, we identified a protein kinase D–interacting substrate of 220 kD (Kidins220)/ankyrin repeat–rich membrane-spanning (ARMS) as novel interaction partner resting stimulated BCR. Upon BCR stimulation, the increases in Src kinase–independent manner. By knocking down Kidins220 line generating conditional cell–specific knockout (B-KO) mouse strain, show that couples to PLCγ2, Ca2+,...
Abstract Detailed knowledge of the human B-cell development is crucial for proper interpretation inborn errors immunity and malignant diseases. It interest to understand kinetics protein expression changes during B cell development, but also properly interpret major possibly alternative developmental trajectories. We have investigated bone marrow peripheral blood samples from healthy individuals with aim describe all trajectories across two tissues. validated a 30-parameter mass cytometry...
Abstract SARS-CoV-2 spike mRNA vaccines mediate protection from severe disease as early 10 days post prime vaccination, when specific antibodies are hardly detectable and still lack neutralizing activity. Vaccine-induced T cells, especially CD8+ may thus be the main mediators of at this stage. The details antigen-specific cell induction after prime/boost their comparison to naturally induced responses association with other arms vaccine-induced adaptive immunity remain, however, incompletely...
Development of T cells is controlled by the signal strength TCR. The scaffold protein kinase D-interacting substrate 220 kilodalton (Kidins220) binds to TCR; however, its role in cell development was unknown. Here, we show that cell-specific Kidins220 knockout (T-KO) mice have strongly reduced invariant natural killer (iNKT) numbers and modest decreases conventional cells. Enhanced apoptosis due increased TCR signaling T-KO iNKT thymocytes developmental stages 2 3 shows down-regulates at...
Primary antiphospholipid syndrome (PAPS) is a life-threatening clotting disorder mediated by pathogenic autoantibodies. Here we dissect the origin of self-reactive B cells in human PAPS using peripheral blood and bone marrow patients with triple-positive via combined single-cell RNA sequencing, cell receptors (BCR) repertoire profiling, CITEseq analysis single immortalization. We find that (aPL)-specific are present naive compartment, polyreactive, derived from natural repertoire....
<h3>Background</h3> Eosinophilic granulomatosis with polyangiitis (EGPA) belongs to the group of ANCA associated vasculitides. While combination asthmatic symptoms and vasculitis characterize disease clinically, eosinophilia increased serum IgE concentrations are serologic hallmarks. The role B lymphocytes in EGPA has not been defined so far, but therapeutic response rituximab points towards a B-cells pathogenesis EGPA. <h3>Objectives</h3> To peripheral cell compartment patients EGPA,...