| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Immunobiology for Research and Diagnosis and Center for Transfusion and Tissue Bank; Institut d’Investigacio Germans Trias i Pujol, Badalona, Barcelona, Spain;
Plataforma de proteomica, Facultat de Medicina, Hospital Clínic, Barcelona, Spain; and
Immunology Unit, Department of Ciencies Mediques Basiques, Faculty of Medicine, University of Lleida, Lleida, Spain
Most of our knowledge of the antigenic repertoire of autoreactive B lymphocytes in type 1 diabetes (T1D) comes from studies on the antigenic specificity of both circulating islet-reactive autoantibodies and peripheral B lymphocyte hybridomas generated from human blood or rodent spleen. In a recent study, we generated hybridoma cell lines of infiltrating B lymphocytes from different mouse strains developing insulitis, but with different degrees of susceptibility to T1D, to characterize the antigenic specificity of islet-infiltrating B lymphocytes during progression of the disease. We found that many hybridomas produced mAbs restricted to the peripheral nervous system (PNS), thus indicating an active B lymphocyte response against PNS elements in the pancreatic islet during disease development. The aim of this study was to identify the autoantigen recognized by these anti-PNS mAbs. Our results showed that peripherin is the autoantigen recognized by all anti-PNS mAbs, and, therefore, a relevant neuroendocrine autoantigen targeted by islet-infiltrating B lymphocytes. Moreover, we discovered that the immune dominant epitope of this B lymphocyte immune response is found at the C-terminal end of Per58 and Per61 isoforms. In conclusion, our study strongly suggests that peripherin is a major autoantigen targeted during T1D development and poses a new question on why peripherin-specific B lymphocytes are mainly attracted to the islet during disease.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a grant from the Fondo de Investigaciones Sanitarias of the Spanish National Institute of Health (FIS 03/0775). M.C.P. was supported by a Severo Ochoa fellowship from the Ferrer Foundation (Barcelona, Spain). A.A. and R.P. were supported by a BEFI Predoctoral Fellowship (01/9065 and 05/0418, respectively) from the Instituto Carlos III of the Spanish National Institute of Health. R.M.A. and X.P. were supported by the Juvenile Diabetes Research Foundation 1-2002-724 Research Grant. M.V.-P. is a researcher at the Fondo de Investigaciones Sanitarias of the Spanish National Institute of Health and the Department of Health of Catalan Government. J.V. is an associate professor of the Serra-Hunter Programme from the Catalan Government.
2 Address correspondence and reprint requests to Dr. Joan Verdaguer, Unitat d’Immunologia, Departament de Ciencies Mediques Basiques, Facultat de Medicina, Universitat de Lleida, Carrer Montserrat Roig 2, 25008 Lleida, Spain. E-mail address: joan.verdaguer{at}cmb.udl.es
3 Abbreviations used in this paper: T1D, type 1 diabetes; PNS, peripheral nervous system; 2-D, two dimensional; IPG, immobilized pH gradient.
This article has been cited by other articles:
|
|
 |
|
  G Song, Y Cui, N Zhong, and J Han Proteomic characterisation of pancreatic islet {beta}-cells stimulated with pancreatic carcinoma cell conditioned medium J. Clin. Pathol., September 1, 2009; 62(9): 802 - 807. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
