While some infections elicit germinal centers, others produce only extrafollicular responses. The mechanisms controlling these dichotomous fates are poorly understood. We identify IL-12 as a cytokine switch, acting directly on B cells to promote extrafollicular and suppress germinal center responses.
View Article and Find Full Text PDFInfection with Borrelia burgdorferi causes Lyme disease in humans. In small rodents, the natural reservoir species of this spirochete, infections lead to only modest disease manifestations, despite causing persistence infection. Although B cell responses are central for controlling bacterial tissue burden and disease manifestations, they lack classical aspects of T-dependent responses, such as sustained IgG affinity maturation and longevity, corresponding with a rapid collapse of germinal centers.
View Article and Find Full Text PDFBoth B cell receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBCs) to synergistically induce c-MYC and phosphorylated S6 ribosomal protein (p-S6), markers of positive selection. How interleukin-21 (IL-21), a key T follicular helper (T)-derived cytokine, affects GCBCs is unclear. Like BCR and CD40 signals, IL-21 receptor (IL-21R) plus CD40 signals also synergize to induce c-MYC and p-S6 in GCBCs.
View Article and Find Full Text PDFKlin Monbl Augenheilkd
December 2022
Background: For quantitative and qualitative evaluation of the imaging properties of IOLs, axial cross-sectional images can be obtained from the 3-dimensional light distribution by means of an optical bench, as is known from light sheet recordings in fluorescein baths. This paper presents a new image-processing algorithm to enhance the quality of generated axial cross-sectional images, and the two methods are then compared.
Material And Methods: The 3-dimensional point spread function of a diffractive trifocal IOL (AT LISA tri 839MP, Carl Zeiss Meditec AG, Jena, Germany) was recorded on an optical bench developed in Rostock for different pupil diameters.
In lupus, Toll-like receptor 7 (TLR7) and TLR9 mediate loss of tolerance to RNA and DNA, respectively. Yet, TLR7 promotes disease, while TLR9 protects from disease, implying differences in signaling. To dissect this 'TLR paradox', we generated two TLR9 point mutants (lacking either ligand (TLR9) or MyD88 (TLR9) binding) in lupus-prone MRL/lpr mice.
View Article and Find Full Text PDFCross-sectional images of three-dimensional point spread functions of intraocular lenses are used to study their image formation. To obtain those, light sheet-based methods are established. Due to the non-negligible thicknesses of the light sheets, the image quality of the cross-sectional images is constrained.
View Article and Find Full Text PDFMemory B cells (MBCs) protect the body from recurring infections. MBCs differ from their naive counterparts (NBCs) in many ways, but functional and surface marker differences are poorly characterized. In addition, although mice are the prevalent model for human immunology, information is limited concerning the nature of homology in B cell compartments.
View Article and Find Full Text PDFActivated B cells participate in either extrafollicular (EF) or germinal center (GC) responses. Canonical responses are composed of a short wave of plasmablasts (PBs) arising from EF sites, followed by GC producing somatically mutated memory B cells (MBC) and long-lived plasma cells. However, somatic hypermutation (SHM) and affinity maturation can take place at both sites, and a substantial fraction of MBC are produced prior to GC formation.
View Article and Find Full Text PDFGerminal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy.
View Article and Find Full Text PDFGerminal centers (GC) are crucial for the formation of long-lived humoral immunity. Many pathogens suppress GC, including Salmonella enterica serovar Typhimurium (STm), but the mechanisms driving suppression remain unknown. We report that neither plasmablasts nor STm-specific B cells are required for GC suppression in mice.
View Article and Find Full Text PDFBehavioural changes that occur during the parr-smolt transformation were investigated in juvenile coho salmon Oncorhynchus kisutch. Fish from two populations were examined from the Fraser River catchment in British Columbia, Canada; a short and a long-distance migrating population. Fish showed a significant decrease in condition factor and significant increase in gill Na K -ATPase activity during the spring indicating that they became competent smolts, but no difference between populations.
View Article and Find Full Text PDFJ Astron Telesc Instrum Syst
April 2019
NASA's Marshall Space Flight Center (MSFC) maintains an active research program toward the development of high-resolution, lightweight, grazing-incidence x-ray optics to serve the needs of future x-ray astronomy missions such as Lynx. MSFC development efforts include both direct fabrication (diamond turning and deterministic computer-controlled polishing) of mirror shells and replication of mirror shells (from figured, polished mandrels). Both techniques produce full-circumference monolithic (primary + secondary) shells that share the advantages of inherent stability, ease of assembly, and low production cost.
View Article and Find Full Text PDFThere is an urgent need for therapeutic agents that target humoral alloimmunity in solid organ transplantation. This includes sensitized patients with preformed donor-specific human leukocyte antigen antibodies and patients who develop de novo donor-specific antibodies, both of which are associated with acute and chronic antibody-mediated rejection and allograft loss. In the last decade, both experimental and clinical studies highlighted the major impact of costimulation molecules in the control of immune responses both in the field of transplantation and autoimmune disease.
View Article and Find Full Text PDFPhysiological changes during the parr-smolt transformation were investigated in short distance (Chilliwack River) and long-distance (Salmon River) migrating coho salmon Oncorhynchus kisutch populations in British Columbia, Canada. Biochemical and molecular indicators were used to monitor smolt development for fish reared at 10 °C throughout the spring. Fish grew well and developed the physical appearance of competent smolts.
View Article and Find Full Text PDFWe report the first Jupiter X-ray observations planned to coincide with an interplanetary coronal mass ejection (ICME). At the predicted ICME arrival time, we observed a factor of ∼8 enhancement in Jupiter's X-ray aurora. Within 1.
View Article and Find Full Text PDFB cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for the prediction of treatment success with immunomodulatory drugs are still missing. Here we evaluated the B cell response to brain antigens in n = 34 relapsing-remitting MS (RRMS) patients treated with glatiramer acetate (GA) using the enzyme-linked immunospot technique (ELISPOT).
View Article and Find Full Text PDFThe B cell response to Salmonella typhimurium (STm) occurs massively at extrafollicular sites, without notable germinal centers (GCs). Little is known in terms of its specificity. To expand the knowledge of antigen targets, we screened plasmablast (PB)-derived monoclonal antibodies (mAbs) for Salmonella specificity, using ELISA, flow cytometry, and antigen microarray.
View Article and Find Full Text PDFLyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B.
View Article and Find Full Text PDFIt is unclear why selective deficiency in secreted (s)IgM causes Ab-mediated autoimmunity. We demonstrate that sIgM is required for normal B cell development and selection. The CD5(+) B cells that were previously shown to accumulate in body cavities of sIgM(-/-) mice are not B-1a cells, but CD19(int), CD43(-), short-lived, BCR signaling-unresponsive anergic B-2 cells.
View Article and Find Full Text PDFCD4 T cells are crucial for enhancing B cell-mediated immunity, supporting the induction of high-affinity, class-switched antibody responses, long-lived plasma cells, and memory B cells. Previous studies showed that the immune response to Borrelia burgdorferi appears to lack robust T-dependent B cell responses, as neither long-lived plasma cells nor memory B cells form for months after infection, and nonswitched IgM antibodies are produced continuously during this chronic disease. These data prompted us to evaluate the induction and functionality of B.
View Article and Find Full Text PDFB cell responses modulate disease during infection with Borrelia burgdorferi, the causative agent of Lyme disease, but are unable to clear the infection. Previous studies have demonstrated that B. burgdorferi infection induces predominantly T-independent B cell responses, potentially explaining some of these findings.
View Article and Find Full Text PDFA transient two-dimensional model describing degenerate four-wave mixing inside saturable gain media is presented. The new model is compared to existing one-dimensional models with their qualitative results confirmed. Large quantitative differences with respect to peak reflectivity and optimum pump fluence are observed.
View Article and Find Full Text PDFWhile diving, seals are exposed to apnea-induced hypoxemia and repetitive cycles of ischemia/reperfusion. While on land, seals experience sleep apnea, as well as prolonged periods of food and water deprivation. Prolonged fasting, sleep apnea, hypoxemia and ischemia/reperfusion increase oxidant production and oxidative stress in terrestrial mammals.
View Article and Find Full Text PDFThe amount of experimental restraints e.g., NOEs is often too small for calculating high quality three-dimensional structures by restrained molecular dynamics.
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