A5054118199- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Vector-borne infectious diseases
- Viral Infections and Vectors
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- Cytokine Signaling Pathways and Interactions
- Yersinia bacterium, plague, ectoparasites research
- Vector-Borne Animal Diseases
- Immunodeficiency and Autoimmune Disorders
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Zoonotic diseases and public health
- Immune responses and vaccinations
- Escherichia coli research studies
- Immune cells in cancer
- Atherosclerosis and Cardiovascular Diseases
- Intensive Care Unit Cognitive Disorders
- Erythrocyte Function and Pathophysiology
- Multiple Sclerosis Research Studies
- CAR-T cell therapy research
- Diabetes and associated disorders
- Cardiac, Anesthesia and Surgical Outcomes
University of Pittsburgh
2015-2025
University of California, Davis
2012-2023
Charité - Universitätsmedizin Berlin
2015
University of Wisconsin–Madison
2007
Both B cell receptor (BCR) and CD40 signaling are rewired in germinal center (GC) cells (GCBCs) to synergistically induce c-MYC phosphorylated S6 ribosomal protein (p-S6), markers of positive selection. How interleukin-21 (IL-21), a key T follicular helper (T FH )–derived cytokine, affects GCBCs is unclear. Like BCR signals, IL-21 (IL-21R) plus signals also synergize p-S6 GCBCs. However, IL-21R stimulation differentially GCBC fate compared with ligation—engaging unique molecular...
Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already far the most common vector-borne in U.S. Similar to many other infections, B. results strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown sometimes-precipitous decline such antibodies shortly following antibiotic treatment, revealing potential deficit host's ability induce and/or maintain...
B cell responses modulate disease during infection with Borrelia burgdorferi, the causative agent of Lyme disease, but are unable to clear infection. Previous studies have demonstrated that B. burgdorferi induces predominantly T-independent responses, potentially explaining some these findings. However, others shown effects T cells on isotype profile and magnitude burgdorferi-specific Abs. This study aimed further investigate humoral response its degree dependence, ultimate goal elucidating...
It is unclear why selective deficiency in secreted (s)IgM causes Ab-mediated autoimmunity. We demonstrate that sIgM required for normal B cell development and selection. The CD5(+) cells were previously shown to accumulate body cavities of sIgM(-/-) mice are not B-1a cells, but CD19(int), CD43(-), short-lived, BCR signaling-unresponsive anergic B-2 cells. Body cavity B-1 >10-fold reduced, including VH11(+) phosphotidylcholine-specific whereas splenic unaffected marginal zone increased....
ABSTRACT CD4 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 cells. Previous studies showed that immune response to Borrelia burgdorferi appears lack robust T-dependent cell as neither nor form months after infection, nonswitched IgM antibodies produced continuously during this chronic disease. These data prompted us evaluate functionality B. infection-induced FH We...
Germinal centers (GC) are crucial for the formation of long-lived humoral immunity. Many pathogens suppress GC, including Salmonella enterica serovar Typhimurium (STm), but mechanisms driving suppression remain unknown. We report that neither plasmablasts nor STm-specific B cells required GC in mice. Rather, we identify interleukin-12 (IL-12), not interferon-γ (IFN-γ), directly suppresses T follicular helper (Tfh) cell differentiation intrinsically. Administering recombinant IL-12 during...
Influenza virus infection results in strong, mainly T-dependent, extrafollicular and germinal center B cell responses, which provide lifelong humoral immunity against the homotypic strain. Follicular T helper cells (T(FH)) are key regulators of immunity. Questions remain regarding presence, identity, function T(FH) subsets regulating early later responses. This study demonstrates that ICOS but not CXCR5 marks with activity induced by influenza identifies (T(GC)) as lymph node-resident CD4(+)...
Abstract Infection with Borrelia burgdorferi causes Lyme disease in humans. In small rodents, the natural reservoir species of this spirochete, infections lead to only modest manifestations, despite causing persistence infection. Although B cell responses are central for controlling bacterial tissue burden and they lack classical aspects T-dependent responses, such as sustained IgG affinity maturation longevity, corresponding a rapid collapse germinal centers. Instead, Ab response is...
Abstract B cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for prediction treatment success with immunomodulatory drugs are still missing. Here we evaluated cell response brain antigens n = 34 relapsing-remitting MS (RRMS) patients treated glatiramer acetate (GA) using enzyme-linked immunospot technique (ELISPOT). Our data demonstrate that can be subdivided into responders show brain-specific reactivity blood and without...
Bacille Calmette Guérin (BCG)-induced granulomas contain T cells that express a broad TCR repertoire even at the level of individual lesion. We have developed BCG infection model in mice having only one cell specific for recombinant epitope expressed lipoprotein fusion protein. Here we report single induces well-formed granulomas, but has weaker protection than conferred by wild-type granulomas. This finding correlates with lower CD4(+) recruitment into acute (3 weeks post infection)....
<h3></h3> In lupus, TLR7 and TLR9 mediate loss of tolerance to RNA DNA, respectively. Yet, promotes while protects from disease, implying differences in signaling. To dissect this 'TLR paradox', we generated two point mutants—lacking either ligand (TLR9K51E) or MyD88 (TLR9P915H) binding—in lupus-prone MRL/lpr mice. Ameliorated disease <i>Tlr9</i>K51E mice compared <i>Tlr9</i>-/- controls revealed a 'scaffold' protective function that is ligand- MyD88-independent. Unexpectedly,...
Abstract While some infections elicit germinal centers (GC), others produce only extrafollicular (EF) 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 EF and suppress GC initiates cell intrinsic feed-forward loop between IFNg, amplifying IFNg production, which promotes proliferation plasmablast (PB) differentiation, in synergy with IL-12. sustains the expression of portion...
Germinal centers (GC) are crucial for the formation of long-lived humoral immunity. Many pathogens suppress GC, including Salmonella enterica serovar Typhimurium (STm), but mechanisms driving suppression remain unknown. Using a mouse model infection, we report that neither plasmablasts, nor even STm-specific B cells were required GC suppression. Rather, uncovered failure in TFH differentiation preceding We identified IL-12, not IFN-γ, suppressed T cell intrinsically. Administering...
<h3>Background</h3> Animal models and more recently studies in humans have implicated the "extrafollicular" (EF) B cell response—rather than germinal center (GC) response—as being prominent possibly pathogenic lupus. This response can also generate so-called "age- associated cells" (ABC, known as "DN2" humans) under some conditions, a type of inflammatory frequency which is elevated lupus patients animal However, basic biology that underlies why immune responses are directed toward EF mode...