Contribution of receptor editing to the antibody repertoire

被引:248
作者
Casellas, R
Shih, TAY
Kleinewietfeld, M
Rakonjac, J
Nemazee, D
Rajewsky, K
Nussenzweig, MC
机构
[1] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA
[2] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
[3] Univ Cologne, Inst Genet, D-50931 Cologne, Germany
[4] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
关键词
D O I
10.1126/science.1056600
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Receptor editing, clonal deletion, and anergy are the mechanisms by which B cells maintain tolerance to self antigens. To determine the extent to which receptor editing shapes the normal antibody repertoire, we generated an immunoglobulin kappa polymorphism that facilitates the detection of;editing of immunoglobulin light chains in vivo. We found that B cells are targeted for editing during a 2-hour delay in development at the pre-BII cell stage, and that about 25% of all antibody molecules are produced by gene replacement. These results suggest that receptor editing represents a major force in shaping the antibody repertoire.
引用
收藏
页码:1541 / 1544
页数:4
相关论文
共 29 条
[1]   ANTIBODY ENGINEERING FOR THE ANALYSIS OF AFFINITY MATURATION OF AN ANTI-HAPTEN RESPONSE [J].
ALLEN, D ;
SIMON, T ;
SABLITZKY, F ;
RAJEWSKY, K ;
CUMANO, A .
EMBO JOURNAL, 1988, 7 (07) :1995-2001
[2]  
ALLMAN DM, 1993, J IMMUNOL, V151, P4431
[3]   Re-evaluation of the probabilities for productive rearrangements on the kappa and lambda loci [J].
Arakawa, H ;
Shimizu, T ;
Takeda, S .
INTERNATIONAL IMMUNOLOGY, 1996, 8 (01) :91-99
[4]   Different sensitivity to receptor editing of B cells from mice hemizygous or homozygous for targeted Ig transgenes [J].
Braun, U ;
Rajewsky, K ;
Pelanda, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (13) :7429-7434
[5]  
BURNET M, 1959, CLONAL SELECTION THE
[6]   Editing disease-associated autoantibodies [J].
Chen, C ;
Prak, EL ;
Weigert, M .
IMMUNITY, 1997, 6 (01) :97-105
[7]   THE SITE AND STAGE OF ANTI-DNA B-CELL DELETION [J].
CHEN, C ;
NAGY, Z ;
RADIC, MZ ;
HARDY, RR ;
HUSZAR, D ;
CAMPER, SA ;
WEIGERT, M .
NATURE, 1995, 373 (6511) :252-255
[8]   ABERRANT REARRANGEMENTS CONTRIBUTE SIGNIFICANTLY TO THE ALLELIC EXCLUSION OF IMMUNOGLOBULIN GENE-EXPRESSION [J].
COLECLOUGH, C ;
PERRY, RP ;
KARJALAINEN, K ;
WEIGERT, M .
NATURE, 1981, 290 (5805) :372-378
[9]   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
[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