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163 results on '"Jungnickel, Berit"'

2. Context-dependent regulation of immunoglobulin mutagenesis by p53

Author

Böttcher, Katrin, Braunschmidt, Kerstin, Hirth, Gianna, Schärich, Karsten, Klassert, Tilman E., Stock, Magdalena, Sorgatz, Janine, Fischer-Burkart, Sabine, Ullrich, Steffen, Frankenberger, Samantha, Kritsch, Daniel, Kosan, Christian, Küppers, Ralf, Strobl, Lothar J., Slevogt, Hortense, Zimber-Strobl, Ursula, and Jungnickel, Berit

Published
2021
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8. Somatic Mutation of the Cd95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction

Author

Müschen, Markus, Re, Daniel, Jungnickel, Berit, Diehl, Volker, Rajewsky, Klaus, and Küppers, Ralf

Subjects
Hematology, Lymphoma, Clinical Research, Rare Diseases, Genetics, Cancer, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Apoptosis, B-Lymphocytes, Cloning, Molecular, DNA Mutational Analysis, Exons, Flow Cytometry, Genes, Tumor Suppressor, Germinal Center, Humans, Immunologic Memory, Mutagenesis, Polymerase Chain Reaction, Protein Structure, Tertiary, Sequence Analysis, Signal Transduction, fas Receptor, CD95, germinal center, B lymphocytes, somatic hypermutation, apoptosis, Medical and Health Sciences, Immunology
Abstract

Somatic hypermutation specifically modifies rearranged immunoglobulin (Ig) genes in germinal center (GC) B cells. However, the bcl-6 gene can also acquire somatic mutations during the GC reaction, indicating that certain non-Ig genes can be targeted by the somatic hypermutation machinery. The CD95 gene, implicated in negative selection of B lymphocytes in GCs, is specifically expressed by GC B cells and was recently identified as a tumor suppressor gene being frequently mutated in (post) GC B cell lymphomas. In this study, the 5' region (5'R) and/or the last exon coding for the death domain (DD) of the CD95 gene were investigated in naive, GC, and memory B cells from seven healthy donors. About 15% of GC and memory, but not naive, B cells carried mutations within the 5'R (mutation frequency 2.5 x 10(-4) per basepair). Mutations within the DD were very rare but could be efficiently selected by inducing CD95-mediated apoptosis: in 22 apoptosis-resistant cells, 12 DD mutations were found. These results indicate that human B cells can acquire somatic mutations of the CD95 gene during the GC reaction, which potentially confers apoptosis resistance and may counteract negative selection through the CD95 pathway.

Published
2000

11. Systemic Candidiasis in Mice: New Insights From an Old Model

Author

Jungnickel, Berit and Jacobsen, Ilse D.

Subjects
General Medicine
Abstract

Animal models are essential to understand the pathophysiology of infections, to test novel antifungal compounds, and to determine the potential of adjunctive therapies, e.g. immune modulation. The murine model of systemic candidiasis induced by intravenous infection is technically straightforward, highly reproducible, and well-characterized. However, intravenous inoculation circumvents the necessity for the fungus to translocate across mucosal barriers, and the use of SPF mice that are immunologically naïve to Candida does not reflect the situation in human patients, in whom adaptive immune responses have been induced by mucosal colonization prior to infection. Therefore, mouse models that combine intestinal colonization and systemic infection have been developed, resulting in novel insights into host-fungal interactions and immunity. In this review, we summarize the main findings, current questions, and discuss how these might impact the translatability of results from mice to humans.

Published
2022

13. Candida albicans Induces Cross-Kingdom miRNA Trafficking in Human Monocytes To Promote Fungal Growth

Author

Halder, Luke D., primary, Babych, Svitlana, additional, Palme, Diana I., additional, Mansouri-Ghahnavieh, Elham, additional, Ivanov, Lia, additional, Ashonibare, Victory, additional, Langenhorst, Daniela, additional, Prusty, Bhupesh, additional, Rambach, Günter, additional, Wich, Melissa, additional, Trinks, Nora, additional, Blango, Matthew G., additional, Kornitzer, Daniel, additional, Terpitz, Ulrich, additional, Speth, Cornelia, additional, Jungnickel, Berit, additional, Beyersdorf, Niklas, additional, Zipfel, Peter F., additional, Brakhage, Axel A., additional, and Skerka, Christine, additional

Published
2022
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19. ERK phosphorylation is RAF independent in naïve and activated B cells but RAF dependent in plasma cell differentiation

Author

Scheffler, Laura, primary, Feicht, Samantha, additional, Babushku, Tea, additional, Kuhn, Laura B., additional, Ehrenberg, Stefanie, additional, Frankenberger, Samantha, additional, Lehmann, Frank M., additional, Hobeika, Elias, additional, Jungnickel, Berit, additional, Baccarini, Manuela, additional, Bornkamm, Georg W., additional, Strobl, Lothar J., additional, and Zimber-Strobl, Ursula, additional

Published
2021
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24. Oligomeric rings of the Sec61p complex induced by ligands required for protein translocation

Author

Hanein, Dorit, Matlack, Kent E.S., Jungnickel, Berit, Plath, Kathrin, Kalies, Kai-Uwe, Miller, Kenneth R., Rapoport, Tom A., and Akey, Christopher W.

Subjects
Translocation (Genetics) -- Research, Endoplasmic reticulum -- Research, Biological sciences
Abstract

Purified mammalian and yeast Sec61p complexes in detergent form cylindrical oligomers with a diameter of approximately 85 angstroms and a central pore of approximately 20 angstroms. These cylindrical oligomers are proposed to represent protein-conducting channels of the endoplasmic reticulum membrane. Through electron microscopy, it was found that each oligomer contains 3-4 heterotrimers. The Sec61p complex's association with ribosomes or the Sec62/63p complex stimulates its oligomer formation.

Published
1996

25. Regulation by the ribosome of the GTPase of the signal-recognition particle during protein targeting

Author

Bacher, Gerald, Lutcke, Henrich, Jungnickel, Berit, Rapoport, Tom A., and Dobberstein, Bernhard

Subjects
Biological transport -- Research, Ribosomes -- Physiological aspects, G proteins -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The promotion of GTP binding to the 54K subunit of signal-recognition particle (SRP) involves a ribosomal component. The SRP helps in the targeting of proteins to the endoplasmic reticulum. High-affinity interaction between SRP and its receptor in the ER membrane is possible in the presence of GTP-bound SRP54. The release of signal sequence from SRP, the placing of the nascent polypeptide chain into the translocation channel and GTP hydrolysis follow the interaction.

Published
1996

26. B Cell Recognition of Candida albicans Hyphae via TLR 2 Promotes IgG1 and IL-6 Secretion for TH17 Differentiation.

Author

Ferreira-Gomes, Marta, Wich, Melissa, Böde, Sally, Hube, Bernhard, Jacobsen, Ilse D., and Jungnickel, Berit

Subjects
CELLULAR recognition, B cells, B cell receptors, CANDIDA albicans, FUNGAL cell walls, FUNGAL growth
Abstract

Candida albicans is usually a benign member of the human gut microbiota, but can become pathogenic under certain circumstances, for example in an immunocompromised host. The innate immune system, in particular neutrophils and macrophages, constitutes a crucial first line of defense against fungal invasion, however adaptive immunity may provide long term protection and thus allow vaccination of at risk patients. While TH1 and TH17 cells are important for antifungal responses, the role of B cells and antibodies in protection from C. albicans infection is less well defined. In this study, we show that C. albicans hyphae but not yeast, as well as fungal cell wall components, directly activate B cells via MyD88 signaling triggered by Toll- like receptor 2, leading to increased IgG1 production. While Dectin-1 signals and specific recognition by the B cell receptor are dispensable for B cell activation in this system, TLR2/MyD88 signals cooperate with CD40 signals in promoting B cell activation. Importantly, recognition of C. albicans via MyD88 signaling is also essential for induction of IL-6 secretion by B cells, which promotes TH17 polarization in T-B cell coculture experiments. B cells may thus be activated directly by C. albicans in its invasive form, leading to production of antibodies and T cell help for fungal clearance. [ABSTRACT FROM AUTHOR]

Published
2021
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27. Impact of Chk1 dosage on somatic hypermutation in vivo.

Author

Bello, Amanda and Jungnickel, Berit

Subjects
*HUMORAL immunity, *DNA damage, *IMMUNOGLOBULIN genes, *DNA repair, *CELL transformation, *B cells, *CHECKPOINT kinase 1
Abstract

Checkpoint signaling in the context of a functional DNA damage response is crucial for the prevention of oncogenic transformation of cells. Our immune system, though, takes the risk of attenuated checkpoint responses during immunoglobulin diversification. B cells undergo continuous DNA damage and error‐prone repair of their immunoglobulin genes during the process of somatic hypermutation. An accompanying attenuation of the DNA damage response via the ATR–Chk1 axis in B cells is believed to allow for a better DNA damage tolerance and for evasion of apoptosis, so as to ensure mutations to be passed on. We sought to determine whether the downregulation of Chk1 could also directly influence the process of hypermutation in vivo by altering the relative activity of error‐prone DNA repair pathways. We analyzed the humoral response and the hypermutation process in mice whose B cells express reduced levels of the Chk1 protein. We found that Chk1 heterozygosity limits the accumulation of mutations in the immunoglobulin loci, likely by impacting on the survival of B cells as they accumulate DNA damage. Nevertheless, we unveiled an unanticipated role for Chk1 downregulation in favoring A/T mutagenesis at the antibody‐variable regions during hypermutation. Even though immunoglobulin mutagenesis was found to be reduced, Chk1 signaling attenuation allows for sustained mutagenesis outside the immunoglobulin loci. Our study thus reveals that a proper Chk1 dosage is crucial for adequate somatic hypermutation in B cells. [ABSTRACT FROM AUTHOR]

Published
2021
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28. A posttargeting signal sequence recognition event in the endoplasmic reticulum membrane

Author

Jungnickel, Berit and Rapoport, Tom A.

Subjects
Endoplasmic reticulum -- Research, Proteins -- Research, Biological sciences
Abstract

The analysis of the initial stages of cotranslational transport of the secretory protein preprolactin through mammalian endoplasmic reticulum (ER) reveals that a translocation substrate undergoes two identification processes before being permitted to go through the ER. After the identification of the signal sequence of the nascent polypeptide chain in the cytosol by the SRP, the chain is shifted to the membrane where a second signal identification step occurs for which the presence in the lipid bilayer of the Sec61p complex is necessary and adequate.

Published
1995

32. The nuclear pore proteins Nup88/214 and T-cell acute lymphatic leukemia–associated NUP214 fusion proteins regulate Notch signaling

Author

Kindermann, Bastian, primary, Valkova, Christina, additional, Krämer, Andreas, additional, Perner, Birgit, additional, Engelmann, Christian, additional, Behrendt, Laura, additional, Kritsch, Daniel, additional, Jungnickel, Berit, additional, Kehlenbach, Ralph H., additional, Oswald, Franz, additional, Englert, Christoph, additional, and Kaether, Christoph, additional

Published
2019
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33. Restriction of AID activity and somatic hypermutation by PARP-1

Author

Tepper, Sandra, primary, Mortusewicz, Oliver, additional, Członka, Ewelina, additional, Bello, Amanda, additional, Schmidt, Angelika, additional, Jeschke, Julia, additional, Fischbach, Arthur, additional, Pfeil, Ines, additional, Petersen-Mahrt, Svend K, additional, Mangerich, Aswin, additional, Helleday, Thomas, additional, Leonhardt, Heinrich, additional, and Jungnickel, Berit, additional

Published
2019
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35. FHR1 triggers the inflammasome and drives sterile inflammation in human diseases

Author

Irmscher, Sarah, primary, Brix, Silke R., additional, Zipfel, Svante L.H., additional, Halder, Luke D., additional, Mutlutürk, Sibel, additional, Cineus, Roodline, additional, Girdaukas, Evaldas, additional, Reichenspurner, Hermann, additional, Stahl, Rolf A.K., additional, Jungnickel, Berit, additional, Wiech, Thorsten, additional, Zipfel, Peter F., additional, and Skerka, Christine, additional

Published
2018
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44. Absence of Immunoglobulin Class Switch in Primary Lymphomas of the Central Nervous System

Author

Montesinos-Rongen, Manuel, primary, Schmitz, Roland, additional, Courts, Cornelius, additional, Stenzel, Werner, additional, Bechtel, Dörte, additional, Niedobitek, Gerald, additional, Blümcke, Ingmar, additional, Reifenberger, Guido, additional, von Deimling, Andreas, additional, Jungnickel, Berit, additional, Wiestler, Otmar D., additional, Küppers, Ralf, additional, and Deckert, Martina, additional

Published
2005
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