Light chain usage in anti-double-stranded DNA B cell subsets: Role in cell fate determination

被引:56
作者
Spatz, L [1 ]
Saenko, V [1 ]
Iliev, A [1 ]
Jones, L [1 ]
Geskin, L [1 ]
Diamond, B [1 ]
机构
[1] YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT MICROBIOL & IMMUNOL, BRONX, NY 10461 USA
关键词
D O I
10.1084/jem.185.7.1317
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Two major mechanisms for the regulation of autoreactive B cells that arise in the bone marrow are functional silencing (anergy) and deletion. Studies to date suggest that low avidity interactions between B cells and autoantigen lead to B cell silencing, whereas high avidity interactions lead to deletion. Anti-double stranded (ds) DNA antibodies represent a pathogenic autospecificity in Systemic Lupus Erythematosus (SLE). An understanding of their regulation is critical to an understanding of SLE. We now demonstrate in a transgenic model in which mice express the heavy chain of a potentially pathogenic anti-DNA antibody that antibody affinity for dsDNA does not alone determine the fate of anti-dsDNA B cells. B cells making antibodies with similar affinities for dsDNA are regulated differently, depending on Light chain usage. A major implication of this observation is that dsDNA may not be the self antigen responsible for cell fate determinations of anti-dsDNA B cells. Light chain usage may determine antigenic crossreactivity, and cross-reactive antigens may regulate B cells that also bind dsDNA.
引用
收藏
页码:1317 / 1326
页数:10
相关论文
共 41 条
[1]   COMPLEXITY OF THE IMMUNOGLOBULIN LIGHT CHAIN V-KAPPA-1 GENE FAMILY IN THE NEW-ZEALAND BLACK MOUSE [J].
BAILEY, NC ;
KASTURI, KN ;
BLACKWELL, TK ;
ALT, FW ;
BONA, CA .
INTERNATIONAL IMMUNOLOGY, 1991, 3 (08) :751-760
[2]  
BERNSTEIN KA, 1995, J IMMUNOL, V154, P2424
[3]  
CORBET S, 1987, J IMMUNOL, V138, P932
[4]   NORMAL MICE EXPRESS IDIOTYPES RELATED TO AUTOANTIBODY IDIOTYPES OF LUPUS MICE [J].
DATTA, SK ;
STOLLAR, BD ;
SCHWARTZ, RS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (09) :2723-2727
[5]   EXPRESSION OF ANTI-DNA IMMUNOGLOBULIN TRANSGENES IN NON-AUTOIMMUNE MICE [J].
ERIKSON, J ;
RADIC, MZ ;
CAMPER, SA ;
HARDY, RR ;
CARMACK, C ;
WEIGERT, M .
NATURE, 1991, 349 (6307) :331-334
[6]   MEASUREMENTS OF THE TRUE AFFINITY CONSTANT IN SOLUTION OF ANTIGEN-ANTIBODY COMPLEXES BY ENZYME-LINKED IMMUNOSORBENT-ASSAY [J].
FRIGUET, B ;
CHAFFOTTE, AF ;
DJAVADIOHANIANCE, L ;
GOLDBERG, ME .
JOURNAL OF IMMUNOLOGICAL METHODS, 1985, 77 (02) :305-319
[7]  
GAVALCHIN J, 1985, J IMMUNOL, V134, P885
[8]   RECEPTOR EDITING - AN APPROACH BY AUTOREACTIVE B-CELLS TO ESCAPE TOLERANCE [J].
GAY, D ;
SAUNDERS, T ;
CAMPER, S ;
WEIGERT, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (04) :999-1008
[9]  
GOODNOW CC, 1992, ANNU REV IMMUNOL, V10, P489, DOI 10.1146/annurev.iy.10.040192.002421
[10]   ALTERED IMMUNOGLOBULIN EXPRESSION AND FUNCTIONAL SILENCING OF SELF-REACTIVE LYMPHOCYTES-B IN TRANSGENIC MICE [J].
GOODNOW, CC ;
CROSBIE, J ;
ADELSTEIN, S ;
LAVOIE, TB ;
SMITHGILL, SJ ;
BRINK, RA ;
PRITCHARDBRISCOE, H ;
WOTHERSPOON, JS ;
LOBLAY, RH ;
RAPHAEL, K ;
TRENT, RJ ;
BASTEN, A .
NATURE, 1988, 334 (6184) :676-682