The immune system plays a critical role in protecting us from infection and resolving or repairing tissue injury following infection or other environmental insults that cause damage. The immune system is also a major contributor to chronic inflammatory diseases that drive health care costs and morbidity and mortality in the U.S., including cardiovascular disease, diabetes, autoimmunity, asthma, transplant rejection and many others. Over the last three decades we have learned much about how immune cells develop and mature, how immune cells are activated and differentiate into ?effector? cells, how immune cell memory is initiated and maintained and how immune cells contribute in a functional way to immune-mediated protection and damage. In this U19 Program, we are particularly interested in B lineage cells that contribute to immune function by presenting antigen and activating CD4 T cells, by altering the immune microenvironment through the production of cytokines and chemokines and, most importantly, by differentiating into short- and long-lived antibody producing plasma cells (ASCs) and long-lived memory B cells. These cells are responsible for the humoral arm of the adaptive immune system and are key to host defense against most viral and bacterial pathogens. However, antibodies produced by ASCs are also responsible for much of the tissue damage associated with autoimmunity, asthma and transplantation. Many of our insights into the protective and pathologic functions of B lymphocytes and ASCs have come from genetically modified mouse model studies and, although these studies have been very informative, it is clear that mice and humans are not identical and that there is a need to better understand how human B cells contribute to immune (dys)function. Our studies of human B cells are still quite rudimentary ? largely because the studies have been limited to the easily accessible circulating blood compartment. This is the equivalent of studying the tail of the elephant without seeing the whole elephant ? we miss most of the complexity and heterogeneity of B cells when we only examine a tiny fraction of the cells that are present in the body. In this U19, we plan to move beyond the elephant tail as our goal is to comprehensively examine the molecular, cellular and functional properties of human B cells that reside specifically in the less accessible human tissues and organs. The major objective of Core A is to provide oversight and support for the overall Program and the individual projects and cores. We will meet this objective by: (i) providing all projects and cores with scientific, administrative, regulatory and financial oversight; and (ii) organizing scientific interactions, including the monthly research in progress meetings for the Program scientists, the annual retreat with the scientific advisory board, the annual meeting with other Cooperative Centers on Human Immunology groups and the Human Immunology themed session at the Southeastern Immunology Symposium. Through these activities, Core A will ensure the overall success of the Program.
