Role of B cell antigen receptor in regulation of V(D)J recombination and cell survival

被引:9
作者
Nemazee, D [1 ]
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
关键词
immune tolerance; B lymphocyte; receptor editing; V(D)J recombination; apoptosis;
D O I
10.1385/IR:21:2-3:259
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
B lymphocytes learn through the interaction of the B cell receptor with antigens in the context of B cell developmental stage and environmental cues. B cells can respond by proliferation and antibody secretion, programmed cell death, or modification of the antibody genes themselves through secondary immunoglobulin gene rearrangements or somatic point mutation. A critical learning process is that of self/nonself-discrimination. We have shown that one potent mechanism for immune self-tolerance in B cells is ongoing antibody light chain gene rearrangements, which can result in "receptor editing" that changes antigen receptor specificity. This process appears to be developmentally regulated, because it is confined to cells at an immature stage of development. Cells at later stages of development can be tolerized by apoptosis, but probably not by receptor editing.
引用
收藏
页码:259 / 263
页数:5
相关论文
共 18 条
  • [1] ORDERED REARRANGEMENT OF IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION SEGMENTS
    ALT, FW
    YANCOPOULOS, GD
    BLACKWELL, TK
    WOOD, C
    THOMAS, E
    BOSS, M
    COFFMAN, R
    ROSENBERG, N
    TONEGAWA, S
    BALTIMORE, D
    [J]. EMBO JOURNAL, 1984, 3 (06) : 1209 - 1219
  • [2] Editing disease-associated autoantibodies
    Chen, C
    Prak, EL
    Weigert, M
    [J]. IMMUNITY, 1997, 6 (01) : 97 - 105
  • [3] Dunda O, 1997, J IMMUNOL, V159, P4362
  • [4] RECEPTOR EDITING - AN APPROACH BY AUTOREACTIVE B-CELLS TO ESCAPE TOLERANCE
    GAY, D
    SAUNDERS, T
    CAMPER, S
    WEIGERT, M
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (04) : 999 - 1008
  • [5] Karasuyama H, 1996, ADV IMMUNOL, V63, P1, DOI 10.1016/S0065-2776(08)60853-6
  • [6] Efficient peripheral clonal elimination of B lymphocytes in MRL/lpr mice bearing autoantibody transgenes
    Kench, JA
    Russell, DM
    Nemazee, D
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (05) : 909 - 917
  • [7] Melamed D, 1997, J IMMUNOL, V159, P1233
  • [8] Self-antigen does not accelerate immature B cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest
    Melamed, D
    Nemazee, D
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (17) : 9267 - 9272
  • [9] Developmental regulation of B lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection
    Melamed, D
    Benschop, RJ
    Cambier, JC
    Nemazee, D
    [J]. CELL, 1998, 92 (02) : 173 - 182
  • [10] MURINE LAMBDA GENE REARRANGEMENTS - THE STOCHASTIC-MODEL PREVAILS OVER THE ORDERED MODEL
    NADEL, B
    CAZENAVE, PA
    SANCHEZ, P
    [J]. EMBO JOURNAL, 1990, 9 (02) : 435 - 440