Development of Type 1 Diabetes despite Severe Hereditary B-Cell Deficiency

Abstract

Type 1 diabetes results from an immune-mediated destruction of pancreatic beta cells. The disease can be transmitted by bone marrow transplantation in humans¹ and animals.^2,3 Furthermore, T cells that are reactive to several islet autoantigens have been identified in both mice and humans.^4,5 Although it is generally accepted that T cells have a role during the disease process, the possible role of B cells and autoantibodies in type 1 diabetes in humans has not been fully resolved. When they are activated, B cells can produce autoantibodies to pancreatic beta-cell antigens — such as glutamic acid decarboxylase 65 (GAD65), insulin, or the tyrosine phosphatase–like autoantigen IA-2 — and are able to take up and present autoantigen to T cells.^6,7