HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thomas, J. W. Articles by Mitchell, H. G. Search for Related Content PubMed PubMed Citation Articles by Thomas, J. W. Articles by Mitchell, H. G.

The Natural Autoantibody Repertoire of Nonobese Diabetic Mice Is Highly Active¹

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232

Analysis of spontaneous hybridomas generated from nonobese diabetic (NOD) mice indicates that the natural autoantibody repertoire of NOD mice is highly active compared with C57BL/6 and BALB/c mice. This property of increased B cell activity is present early in life (4 wk) and persists in older mice of both sexes. Even when selected for binding to a prototypic cell Ag, such as insulin, NOD mAb have characteristics of natural autoantibodies that include low avidity and broad specificity for multiple Ags. Analyses of the variable region of Ig H chain (V_H) and variable region L chain genes expressed by six insulin binding mAb show that V gene segments are often germline encoded and are identical with those used by autoantibodies, especially anti-dsDNA, from systemic autoimmune disease in MRL, NZB/W, and motheaten mice. V_H genes used by four mAb are derived from the large J558 family and two mAb use V_H7183 and V_HQ52 genes. The third complementarity-determining region of Ig H chain of these mAb have limited N segment diversity, and some mAb contain DNA segments indicative of gene replacement. Genetic abnormalities in the regulation of self-reactive B cells may be a feature that is shared between NOD and conventional systemic autoimmune disorders. In NOD, the large pool of self-reactive B cells may fuel autoimmune cell destruction by facilitating T-B cell interactions, as evidenced by the identification of one mAb that has undergone Ag-driven somatic hypermutation.

This article has been cited by other articles:

				R. Ekici, M. Sundstrom, B. Thay, and K. Lejon Enhanced capture of extramembranous IgM and IgG on B cells in the NOD mouse--implications for immune complex trapping Int. Immunol., May 1, 2009; 21(5): 533 - 541. [Abstract] [Full Text] [PDF]

				H. Bour-Jordan, B. L. Salomon, H. L. Thompson, R. Santos, A. K. Abbas, and J. A. Bluestone Constitutive Expression of B7-1 on B Cells Uncovers Autoimmunity toward the B Cell Compartment in the Nonobese Diabetic Mouse J. Immunol., July 15, 2007; 179(2): 1004 - 1012. [Abstract] [Full Text] [PDF]

				E. J. Woodward and J. W. Thomas Multiple Germline {kappa} Light Chains Generate Anti-Insulin B Cells in Nonobese Diabetic Mice J. Immunol., July 15, 2005; 175(2): 1073 - 1079. [Abstract] [Full Text] [PDF]

				D. Sblattero, F. Maurano, G. Mazzarella, M. Rossi, S. Auricchio, F. Florian, F. Ziberna, A. Tommasini, T. Not, A. Ventura, et al. Characterization of the Anti-Tissue Transglutaminase Antibody Response in Nonobese Diabetic Mice J. Immunol., May 1, 2005; 174(9): 5830 - 5836. [Abstract] [Full Text] [PDF]

				J. Carrillo, M. C. Puertas, A. Alba, R. M. Ampudia, X. Pastor, R. Planas, N. Riutort, N. Alonso, R. Pujol-Borrell, P. Santamaria, et al. Islet-infiltrating B-Cells in Nonobese Diabetic Mice Predominantly Target Nervous System Elements Diabetes, January 1, 2005; 54(1): 69 - 77. [Abstract] [Full Text] [PDF]

				F. S. Wong, L. Wen, M. Tang, M. Ramanathan, I. Visintin, J. Daugherty, L. G. Hannum, C. A. Janeway Jr, and M. J. Shlomchik Investigation of the Role of B-Cells in Type 1 Diabetes in the NOD Mouse Diabetes, October 1, 2004; 53(10): 2581 - 2587. [Abstract] [Full Text] [PDF]