Grant Details

Description

The presence of lymphocytic populations in the inflamed tissue of patients with autoimmune diseases suggests that self-antigens drive the disease process. In this regard, type 1 autoimmune diabetes (T1D) is characterized by the presence of lymphocytic infiltrates in the islets of Langerhans, leading to the destruction of islet b cells. Among the autoimmune diseases in humans, diabetes is unique as it can be predicted before the onset of clinical disease in first-degree relatives by the presence of two or more antibodies reactive to islet cell antigens. B cells are responsible for the production and secretion of antibodies. The contributions of B cells and their secreted products to T cell responses and the recent observations of dramatic responses to B cell depleting therapy in patients with rheumatoid arthritis and MS provide compelling evidence for a role of B cells in the pathogenesis of human autoimmune diseases. In addition to antibodies, B cells secrete cytokines (proteins made by cells for cellular communication), express T cell stimulation molecules, and can act as antigen presenting cells to activate T cells with the same antigen specificity and contribute to the amplification of the immune response. We will interrogate and correlate the three major functions of B cells in T1D: autoantibody secretion, cytokine secretion and autoantigen presentation to determine how they drive T cells to an inflammatory effector response. The approach will be to identify and retrieve B cells secreting auto-reactive antibodies from peripheral blood using a new technology which allows rapid, high-throughput screening of >100,000 single cells for the multiplexed examination of cytokine secretion, cell surface determinants, antigen specific immunoglobulins, and the DNA sequence of the antibody protein.

StatusFinished
Effective start/end date09/1/0908/31/12

Funding

  • Juvenile Diabetes Research Foundation United States of America: $270,000.00

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