T-Bet Expressing B Cells With Distinct Residency And Functional Characteristics Give Rise To Plasma Cells

An increasing body of work shows that T-bet+ B cells play important roles in immune responses to infections a well as in autoimmune diseases. These studies investigate the kinetics, tissue distribution, and functions of T-bet+ B cells in a murine influenza infection model. Both T-bet+ and T-bet- HA-specific B cells emerge early after infection, acquire the memory markers CD73, PD-L2 and CD80, and persist indefinitely with limited interconversion between T-bet+ and T-bet- B cell pools. Moreover, T-bet+ B cells are required for HA stalk specific antibodies and sustained protective HAI titers. T-bet+ HA-specific B cells can be further divided into T-bethigh and T-betlow B cell pools. While T-bethigh, T-betlow, and T-bet- HA-specific B cells are initially found in the spleen, lungs, and draining mediastinal lymph nodes; at later timepoints T-bethigh HA-specific memory B cells are restricted to the spleen, despite the continued presence of T-bet- HA-specific B cells at other anatomical locations. Parabiotic studies show that HA-specific T-bethigh B cells are splenic residents, whereas T-betlow and T-bet- B cells recirculate. T-bethigh B cells give rise to T-betlow B cells but T-betlow B cells do not become T-bethigh. However, T-betlow B cells persist for a minimum of three weeks in the absence of T-bethigh B cells, indicating that they are likely distinct populations. CD138 levels increase with decreasing T-bet expression and T-betlow and T-bethigh B cells downregulate T-bet and give rise to plasma cells. Both B220+ and B220- plasma cells arise from T-bet+ B cells in the spleen and bone marrow. Together, these data suggest that T-bethigh memory B cells are a unique splenic resident population with stem cell like properties that sustains plasma cell numbers and protective antibody titers long term

National Leadership Index 2009: A National Study of Confidence in Leadership

The National Study of Confidence in Leadership is a social science research program examining the attitudes of the American public toward the nation’s leadership. The study includes the National Leadership Index 2009, a multidimensional measure of the public’s confidence in leadership within different sectors of society.Center for Public Leadershi

Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective degeneration of motor neurons, atrophy, and paralysis of skeletal muscle. Although a significant proportion of familial ALS results from a toxic gain of function associated with dominant SOD1 mutations, the etiology of the disease and its specific cellular origins have remained difficult to define. Here, we show that muscle-restricted expression of a localized insulin-like growth factor (Igf) -1 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1G93A transgenic mice, inducing calcineurin-mediated regenerative pathways. Muscle-specific expression of local Igf-1 (mIgf-1) isoform also stabilized neuromuscular junctions, reduced inflammation in the spinal cord, and enhanced motor neuronal survival in SOD1G93A mice, delaying the onset and progression of the disease. These studies establish skeletal muscle as a primary target for the dominant action of inherited SOD1 mutation and suggest that muscle fibers provide appropriate factors, such as mIgf-1, for neuron survival

National Leadership Index 2006: A National Study of Confidence in Leadership

The National Leadership (NSCL) is a social science research program examining the attitudes of the American public toward the nation’s leadership. The study includes the National Leadership Index 2006 (NLI), a multidimensional measure of the public’s confidence in the leadership of different sectors of society.US News & World Report, Center for Public Leadershi