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.
|D'Angio, Carl T; Wyman, Claire P; Misra, Ravi S et al. (2017) Plasma cell and serum antibody responses to influenza vaccine in preterm and full-term infants. Vaccine 35:5163-5171|
|Bouta, Echoe M; Kuzin, Igor; de Mesy Bentley, Karen et al. (2017) Brief Report: Treatment of Tumor Necrosis Factor-Transgenic Mice With Anti-Tumor Necrosis Factor Restores Lymphatic Contractions, Repairs Lymphatic Vessels, and May Increase Monocyte/Macrophage Egress. Arthritis Rheumatol 69:1187-1193|
|Bird, Anna K; Chang, Martin; Barnard, Jennifer et al. (2017) Neutrophils Slow Disease Progression in Murine Lupus via Modulation of Autoreactive Germinal Centers. J Immunol 199:458-466|
|Rangel-Moreno, Javier; To, Jesi Y; Owen, Teresa et al. (2016) Inhibition of G Protein ?? Subunit Signaling Abrogates Nephritis in Lupus-Prone Mice. Arthritis Rheumatol 68:2244-56|
|Kuzin, Igor I; Kates, Stephen L; Ju, Yawen et al. (2016) Increased numbers of CD23(+) CD21(hi) Bin-like B cells in human reactive and rheumatoid arthritis lymph nodes. Eur J Immunol 46:1752-7|
|Meednu, Nida; Zhang, Hengwei; Owen, Teresa et al. (2016) Production of RANKL by Memory B Cells: A Link Between B Cells and Bone Erosion in Rheumatoid Arthritis. Arthritis Rheumatol 68:805-16|
|Halliley, Jessica L; Tipton, Christopher M; Liesveld, Jane et al. (2015) Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow. Immunity 43:132-45|
|Bouta, Echoe M; Li, Jie; Ju, Yawen et al. (2015) The role of the lymphatic system in inflammatory-erosive arthritis. Semin Cell Dev Biol 38:90-7|
|Tipton, Christopher M; Fucile, Christopher F; Darce, Jaime et al. (2015) Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat Immunol 16:755-65|
|Newell, K A; Asare, A; Sanz, I et al. (2015) Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients. Am J Transplant 15:2908-20|
Showing the most recent 10 out of 56 publications