|
|
||||||||
The Journal of Immunology, Vol 159, Issue 4 1728-1738, Copyright © 1997 by American Association of Immunologists
ARTICLES |
JJ Stewart, H Agosto, S Litwin, JD Welsh, M Shlomchik, M Weigert and PE Seiden
Department of Molecular Biology, Princeton University, NJ 08544, USA.
Rheumatoid factors (RF) associated with arthritic joint erosion are only seen transiently, if at all, in nondiseased individuals. Therefore, a tolerance mechanism must exist that prevents pathologic RF B cells from expressing Abs. Surprisingly, it has been shown that pathologic RF B cells are not tolerized by any previously established tolerance mechanism such as deletion, receptor editing, anergy, or prevention of memory establishment. How are pathologic RF cells tolerized? By simulating the RF response with a cellular automaton model immune system, we demonstrate that pathologic RFs can be tolerized by the novel mechanism of "competitive tolerance" with natural, nonpathologic RFs. We then demonstrate that competitive tolerance can be broken when a sequestered pool of expanding B cells are inappropriately subjected to chronic stimulation (as appears to occur in MRL/lpr mice and in patients with rheumatoid arthritis).
This article has been cited by other articles:
![]() |
N. Milosevic-Jovcic, D. Ciric, L. Hajdukovic-Dragojlovic, and V. Mircetic Differences in the relationship of specificity to titre and functional affinity between circulating Ga- and pan-reactive IgM rheumatoid factors in rheumatoid arthritis Rheumatology, September 1, 2004; 43(9): 1190 - 1193. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H. Roark, J. B. Bussel, D. B. Cines, and D. L. Siegel Genetic analysis of autoantibodies in idiopathic thrombocytopenic purpura reveals evidence of clonal expansion and somatic mutation Blood, July 30, 2002; 100(4): 1388 - 1398. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Ehrenstein, H. T. Cook, and M. S. Neuberger Deficiency in Serum Immunoglobulin (Ig)M Predisposes to Development of IgG Autoantibodies J. Exp. Med., April 3, 2000; 191(7): 1253 - 1258. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Dong, W. J. Storkus, and R. D. Salter Binding and Uptake of Agalactosyl IgG by Mannose Receptor on Macrophages and Dendritic Cells J. Immunol., November 15, 1999; 163(10): 5427 - 5434. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Jemmerson, J. M. Minnerath, S. M. Hedrick, and S. Oehen B Cell Tolerance to a Minor, But Not to a Major, Antigenic Surface of the Self Antigen, Cytochrome c J. Immunol., September 15, 1998; 161(6): 2841 - 2847. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |