B cells are critical players in the orchestration of properly regulated immune responses that provide protection against infectious agents without inflicting auto-inflammatory damage. Achieving this physiological balance requires the finely regulated participation of multiple B cell populations with different antibody dependent and independent functions. This is a rather precarious balance since, as demonstrated by multiple studies, since B cells also mediate powerful pro-inflammatory effector functions which if unchecked contribute to the pathogenesis of multiple pathological conditions of great impact in the health of the population including multiple autoimmune conditions, transplant rejection, atherosclerosis, defective cancer surveillance, COPD, asthma and liver fibrosis. The complexity and clinical relevance of B cells has also been brought to the fore in recent years by the success of Rituximab-based B cell depletion therapy (BCDT) in multiple autoimmune diseases. It is therefore apparent that understanding the phenotypic heterogeneity and functional division of labor among different B cell populations will be critical to unravel the pathophysiology of autoimmune diseases and other major clinical conditions. This central goal will be accomplished through the interactive work of 4 projects and two major cores under the administrative oversight provided by Core A;Project 1: Human transitional B cells: homeostasis, function and impact of BCDT;Project 2: Human effector B cells: homeostasis, function and regulation in SLE;Project 3: Evaluation of IFNg-producing effector B cells in infectious and autoimmune disease;Project 4: Role of B cells in Synovial Inflammation and Lymph Node Remodeling in Inflammatory Arthritis;Core B: Coordinating Clinical Core;and Core C: Biostatistics and Data Management Core. The knowledge derived from the work proposed in this PPG should also enable investigators to better design and evaluate vaccine responses. Finally, and central to this PPG, our results will greatly enhance our ability to design better and safer BCDT therapies and to develop biomarkers of B cell targeted treatments efficacy and safety.
Understanding the proper balance of protective and deleterious B cell functions is ofthe outmost importance for understanding and treating multiple autoimmune diseases such as Lupus, Rheumatoid Arthritis, Diabetes and Multipie Sclerosis. This knowledge would also greatly help in designing and evaluating vaccines. This PPG brings together a group of talented B cell scientists and clinicians to evaluate in a synergistic and complementary way the identify and function of several new B cell populations and their role in disease suing human diseases as well as appropriate animal models for these diseases.
|Bouta, Echoe M; Banik, Peony D; Wood, Ronald W et al. (2015) Validation of power Doppler versus contrast-enhanced magnetic resonance imaging quantification of joint inflammation in murine inflammatory arthritis. J Bone Miner Res 30:690-4|
|León, Beatriz; Ballesteros-Tato, André; Randall, Troy D et al. (2014) Prolonged antigen presentation by immune complex-binding dendritic cells programs the proliferative capacity of memory CD8 T cells. J Exp Med 211:1637-55|
|Sanz, Iñaki (2014) Rationale for B cell targeting in SLE. Semin Immunopathol 36:365-75|
|Wang, Wensheng; Rangel-Moreno, Javier; Owen, Teresa et al. (2014) Long-term B cell depletion in murine lupus eliminates autoantibody-secreting cells and is associated with alterations in the kidney plasma cell niche. J Immunol 192:3011-20|
|Palanichamy, Arumugam; Bauer, Jason W; Yalavarthi, Srilakshmi et al. (2014) Neutrophil-mediated IFN activation in the bone marrow alters B cell development in human and murine systemic lupus erythematosus. J Immunol 192:906-18|
|Finak, Greg; Jiang, Wenxin; Krouse, Kevin et al. (2014) High-throughput flow cytometry data normalization for clinical trials. Cytometry A 85:277-86|
|Bouta, Echoe M; Wood, Ronald W; Brown, Edward B et al. (2014) In vivo quantification of lymph viscosity and pressure in lymphatic vessels and draining lymph nodes of arthritic joints in mice. J Physiol 592:1213-23|
|León, Beatriz; Bradley, John E; Lund, Frances E et al. (2014) FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability. Nat Commun 5:3495|
|Zhang, Hengwei; Hilton, Matthew J; Anolik, Jennifer H et al. (2014) NOTCH inhibits osteoblast formation in inflammatory arthritis via noncanonical NF-?B. J Clin Invest 124:3200-14|
|Roberts, Mustimbo E P; Kaminski, Denise; Jenks, Scott A et al. (2014) Primary Sjögren's syndrome is characterized by distinct phenotypic and transcriptional profiles of IgD+ unswitched memory B cells. Arthritis Rheumatol 66:2558-69|
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