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Studies of the reaction of antibody A2B5 and tetanus toxin with pancreatic islet cells, islet cell tumors, and other human amine precursor uptake and decarboxylation (APUD) tumors are described. By indirect immunofluorescence, antibody A2B5 and tetanus toxin were shown to specifically bind to the plasma membrane of human, rat, chicken, and mouse islet cells. The binding of antibody A2B5 to the cell surface ofliving islet cells has allowed isolation of these cells from a suspension ofpancreatic cells by using a fluorescence-activated cell sorter. In studies designed to determine whether tetanus toxin and antibody A2B5 bound to the same surface antigen, A2B5 and tetanus toxin did not compete for binding to normal islet cells, a human islet cell tumor, or a rat islet cell tumor. In addition to binding to islet cell tumors, antibody A2B5 reacts with frozen sections, isolated cells, and cell lines of neural, neural crest, and APUD origin.The acronym APUD (amine precursor uptake and decarboxylation) was attached in 1968 to a series of cells that have common cytochemical properties, in particular their amine-handling characteristics (1). The APUD series includes pancreatic islet, adrenomedullary, enterochromaffin, anterior pituitary, and thyroid C cells. It was hypothesized that these diverse cell types were all ofneural crest origin. Although some controversy persists (1), recent evidence, including grafts of quail neural primordium and chicken embryos (2-4), demonstration of APUD cells in the gut groove at 16-to 18-somite stages (5), and transplantation studies (6, 7), indicates that pancreatic islet cells are not of neural crest origin but arise from the endoderm. It is noteworthy that these same techniques confirm a neural crest origin for avian thyroid C cells (8). Despite this difference in embryonic derivation, neurons and pancreatic islet cells share many metabolic pathways (e.g., APUD), release a number of identical peptides (e.g., somatostatin and glucagon), and express neurone-specific enolase (9). Little is known, however, concerning the expression of similar cell surface differentiation antigens by islet cells and neurons. Recently, the techniques developed by Kohler and Milstein for the production of lymphocyte hybridomas (10) have been used to produce monoclonal antibodies reacting with a variety of cell surface differentiation antigens (11). In the present study, we use two "neuronal" markers that react with specific gangliosides, monoclonal antibody A2B5 and tetanus toxin, to test the hypothesis that islet cells and neurons express similar cell surface antigens. METHODS AND MATERIALSProduction of Monoclonal Antibody A2B5. Antibody F12 A2B5 was produced in ascites fluid of BALB/c mice by clone 105, which has been donated to the American Type Culture Collection (12).Cells. RINm5f and RINm14B rat insulinoma cell lines were kindly supplied by A. Gazdar, H. Oie, and W. Chick (13). Viable islet cells were isolated from chicken pancreas by mincing the pancreas with a fine scissor followed by collagen...

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The Ia (immune-associated, DR) antigen is a cell surface glycoprotein which is absent on normal circulating T lymphocytes but present on activated T lymphocytes. We studied the expression of this antigen on circulating T lymphocytes from patients with untreated hyperthyroid Graves' disease. All patients (n = 33) with recent onset hyperthyroid Graves' disease studied had an increased percentage and number of circulating Ia+ T cells. Patients with non-Graves's hyperthyroidism or Graves' disease patients more than 1 yr after thyroid ablation had normal values for Ia+ T cells. Other cell surface activation antigens, recognized by monoclonal antibodies 4F2 and 5E9, were not present on circulating T cells in patients with Graves' disease. The 100% positivity for increased numbers of Ia antigen-bearing T cells in hyperthyroid Graves' disease contrasts with our finding of 70% positivity in another HLA-DR-associated disease, recent onset type I diabetes mellitus. The pathogenic significance of these cells is not known, but they seem to represent selective activation of the immune system in patients with untreated hyperthyroid Graves' disease.