DOI: 10.2337/db06-0428 © 2007 by the American Diabetes Association Phenotype and Functional Characteristics of Islet-Infiltrating B-Cells Suggest the Existence of Immune Regulatory Mechanisms in Islet Milieu
1 Laboratory of Immunobiology for Research and Diagnosis (LIRAD) and Center for Transfusion and Tissue Bank (BST), Institut d'Investigacio Germans Trias i Pujol, Carretera de Can Ruti, Badalona, Barcelona, Spain Address correspondence and reprint requests to Dr. Joan Verdaguer, Unit of Immunology, Departament de Ciencies Mediques Basiques, Facultat de Medicina, Universitat de Lleida, Carrer Montserrat Roig 2, 25008 Lleida, Catalonia, Spain. E-mail: joan.verdaguer{at}cmb.udl.es
Abbreviations:
APC, antigen-presenting cell; CFSE, carboxy-fluorescein diacetate succinimidyl ester; CTL, cytotoxic T-cell; FITC, fluorescein isothiocyanate; IFN-
B-cells participate in the autoimmune response that precedes the onset of type 1 diabetes, but how these cells contribute to disease progression is unclear. In this study, we analyzed the phenotype and functional characteristics of islet-infiltrating B-cells in the diabetes-prone NOD mouse and in the insulitis-prone but diabetes-resistant (NODxNOR)F1 mouse. The results indicate that B-cells accumulate in the islets of both mice influenced by sex traits. Phenotypically and functionally, these B-cells are highly affected by the islet inflammatory milieu, which may keep them in a silenced status. Moreover, although islet-infiltrating B-cells seem to be antigen experienced, they can only induce islet-infiltrating T-cell proliferation when they act as accessory cells. Thus, these results strongly suggest that islet-infiltrating B-cells do not activate islet-infiltrating T-cells in situ, although they may affect the progression of the disease otherwise.
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