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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI078907-05
Application #
8707312
Study Section
Special Emphasis Panel (ZAI1-PA-I (J1))
Program Officer
Peyman, John A
Project Start
2010-08-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
$2,188,962
Indirect Cost
$266,617
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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