A5014570970- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- PI3K/AKT/mTOR signaling in cancer
- Calcium signaling and nucleotide metabolism
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Immune Response and Inflammation
- Toxin Mechanisms and Immunotoxins
- Chronic Lymphocytic Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Cell Adhesion Molecules Research
- Protein Tyrosine Phosphatases
- Tuberous Sclerosis Complex Research
- Adenosine and Purinergic Signaling
- Multiple Myeloma Research and Treatments
- Blood disorders and treatments
- Protein Kinase Regulation and GTPase Signaling
- Peptidase Inhibition and Analysis
- Genomics, phytochemicals, and oxidative stress
- Kruppel-like factors research
- Renal and related cancers
- Acute Myeloid Leukemia Research
- Natural product bioactivities and synthesis
University of Freiburg
2015-2025
University Medical Center Freiburg
2024-2025
Max Planck Institute of Immunobiology and Epigenetics
2013-2019
Binding of antigen to the B cell receptor (BCR) initiates a multitude events resulting in activation. How BCR becomes signaling-competent upon binding is still matter controversy. Using high-resolution proximity ligation assay (PLA) monitor conformation and its interactions with co-receptors at 10–20 nm resolution, we provide direct evidence for opening dimers during We also show that Syk opens by an inside-out signaling mechanism amplifies signaling. Furthermore, found on resting cells,...
Significance Worldwide about one million patients are given anti-CD20 antibodies such as rituximab (RTX) for the treatment of B cell-associated diseases. Despite success this first therapeutic antibody, little is known function its target. The role CD20 only becomes clear in context nanoscale compartmentalization lymphocyte membrane. We found that an organizer IgD-class nanocluster on cell loss human cells results a dissolution and transient activation inducing cell-to-PC differentiation....
Article18 April 2018Open Access Transparent process Continuous signaling of CD79b and CD19 is required for the fitness Burkitt lymphoma B cells Xiaocui He orcid.org/0000-0002-0106-057X BIOSS Centre For Biological Signaling Studies, Department Molecular Immunology, Biology III, Faculty Biology, University Freiburg, Germany Max Planck Institute Immunobiology Epigenetics, Search more papers by this author Kathrin Kläsener orcid.org/0000-0002-5969-2553 Joseena M Iype Martin Becker...
CD38 is a multifunctional protein expressed on the surface of B cells in healthy individuals but also cell malignancies. Previous studies have suggested connection between and components IgM class antigen receptor (IgM-BCR) its coreceptor complex. Here, we provide evidence that closely associated with CD19 resting IgM-BCR upon engagement. We show targeting an antibody, or removing this molecule CRISPR/Cas9, inhibits association IgM-BCR, impairing BCR signaling normal malignant cells....
In mice, neonatally-developing, self-reactive B-1 cells generate steady levels of natural antibodies throughout life. can, however, also rapidly respond to infections with increased local antibody production. The mechanisms regulating these two seemingly very distinct functions are poorly understood, but have been linked expression CD5, an inhibitor BCR-signaling. Here we demonstrate that TLR-mediated activation CD5+ induced the rapid reorganization IgM-BCR complex, leading eventual loss CD5...
Abstract Siglec-G is an inhibitory receptor on B1 cells. Siglec-G–deficient mice show a large cell expansion, owing to higher BCR-induced Ca2+ signaling and enhanced cellular survival. It was unknown why shows cell–restricted function. With new mAb we could comparable expression cells conventional B2 However, has different ligand sialic acid–binding pattern peritoneal than splenic B cells, its acid ligands are expressed differentially these two populations, suggesting that cis-ligand binding...
CD20 is a four-transmembrane protein expressed at the surface of B cells from late pro-B to memory cells, with exception plasma cells. Its expression pattern makes it an attractive therapeutic target for different cell malignancies and autoimmune diseases. Despite clinical success CD20-targeting antibodies, biology still not well understood. We investigated binding partners in membrane human using immunoprecipitation followed by mass spectrometry analysis. identified molecular interaction...
Abstract Signal transduction from the BCR is regulated by equilibrium between kinases (e.g., spleen tyrosine kinase [Syk]) and phosphatases Shp-1). Previous studies showed that Syk-deficient B cells have a developmental block at pro/pre–B cell stage, whereas cell–specific Shp-1 deficiency promoted B-1a development led to autoimmunity. We generated Syk double-knockout (DKO) mice compared them single-knockout deficient for either or Shp-1. Unlike mice, DKO can generate mature cells, albeit...
Abstract The invariant chain (CD74), a chaperone in MHC class II–mediated Ag presentation, is sequentially processed by different endosomal proteases. We reported recently that clearance of the final membrane-bound N-terminal fragment (NTF) CD74 mediated intramembrane protease signal peptide peptidase-like (SPPL)2a, process critical for B cell development. In mice, SPPL2a deficiency provokes accumulation this NTF endocytic vesicles, which leads to maturation arrest at transitional 1 stage....
Abstract FLT3-ITD is the most predominant mutation in AML being expressed about one-third of patients and associated with a poor prognosis. Efforts to better understand downstream signaling possibly improve therapy response are needed. We have previously described FLT3-ITD-dependent phosphorylation CSF2RB, common receptor beta chain IL-3, IL-5, GM-CSF, therefore examined its significance for oncogenic transformation. discovered that directly binds CSF2RB cell lines blasts isolated from...
The survival and proliferation of CLL cells depends on microenvironmental contacts in lymphoid organs. CD38 is a cell surface receptor that plays an important role signaling CLL. In this study we demonstrate SYK's direct involvement the pathway primary samples. stimulation revealed SYK activation. downstream target AKT was subsequently induced MCL-1 expression increased. Concomitant inhibition by inhibitor R406 resulted reduced activation prevented upregulation MCL-1. Moreover, short-term...
B cell antigen receptor (BCR) signaling is initiated by protein kinases and limited counteracting phosphatases that currently are less well studied in their regulation of BCR signaling. Here, we used the line Ramos to identify quantify human components. Specifically, a tyrosine phosphatase profiling revealed high expression 1B (PTP1B) naïve cells. The loss PTP1B leads increased activation. Through substrate trapping combination with quantitative mass spectrometry, identified 22 putative...
Abstract Background Pediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin's B-cell lymphoma. Despite encouraging survival rates for children, treating cases with relapse and resistance to current therapies remains challenging. CD38, a transmembrane protein highly expressed in pBL, promising therapeutic target. This study investigates effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab (DARA) isatuximab (ISA), impairing crucial cellular processes...
The early transcription unit 3 (E3) of human adenoviruses (HAdVs) encodes several immunoevasins, including the E3/49K protein, which is unique for species D HAdVs. It expressed as surface transmembrane protein and shed. HAdV-D64 binds to tyrosine phosphatase receptor CD45, thereby modulating activation T NK cells.
Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite encouraging survival rates for children, treating cases with relapse/resistance to current therapies remains challenging. CD38 a transmembrane protein highly expressed in pBL. This study investigates effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, impairing crucial cellular processes pathways pBL malignant cells.
ABSTRACT B cell antigen receptor (BCR) signaling is initiated by protein kinases and limited counteracting phosphatases that currently are less well studied in their regulation of BCR signaling. We here used the line Ramos to identify quantify human components. Specifically, a tyrosine phosphatase profiling revealed high expression 1B (PTP1B) naïve cells. The loss PTP1B leads increased activation. Through substrate trapping combination with quantitative mass spectrometry, we identified 22...