The mechanisms of immune diversification and their disorders

被引：48

作者：

de Villartay, JP ^{[1
]}

Fischer, A ^{[1
]}

Durandy, A ^{[1
]}

机构：

[1] Hop Necker Enfants Malad, INSERM, U429, F-75015 Paris, France

来源：

NATURE REVIEWS IMMUNOLOGY | 2003年 / 3卷 / 12期

关键词：

D O I：

10.1038/nri1247

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Three molecular mechanisms contribute to the diversity of the immune repertoire of B and T cells: V(D)J recombination generates the primary repertoire in both cases, whereas class-switch recombination (CSR) and somatic hypermutation (SHM) improve the quality of the B-cell response after antigen triggering. These three mechanisms involve marked DNA damage and modification, which require a fully competent cellular DNA-repair machinery. Defects in V(D)J recombination, CSR or SHM reactions lead to immune deficiencies, the study of which has allowed the identification of genes that are central to these processes. The inability to properly manage DNA damage/modification during V(D)J recombination, can also promote the development of cancer, as shown by the emergence of B-cell lymphomas in patients with a partial Artemis defect.

引用

页码：962 / 972

页数：11

共 130 条

[1] THE PHD FINGER - IMPLICATIONS FOR CHROMATIN-MEDIATED TRANSCRIPTIONAL REGULATION [J].

AASLAND, R ;

GIBSON, TJ ;

STEWART, AF .

TRENDS IN BIOCHEMICAL SCIENCES, 1995, 20 (02) :56-59

[2] Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice [J].

Akamatsu, Y ;

Monroe, R ;

Dudley, DD ;

Elkin, SK ;

Gärtner, F ;

Talukder, SR ;

Takahama, Y ;

Alt, FW ;

Bassing, CH ;

Oettinger, MA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (03) :1209-1214

[3] CD40 LIGAND GENE DEFECTS RESPONSIBLE FOR X-LINKED HYPER-IGM SYNDROME [J].

ALLEN, RC ;

ARMITAGE, RJ ;

CONLEY, ME ;

ROSENBLATT, H ;

JENKINS, NA ;

COPELAND, NG ;

BEDELL, MA ;

EDELHOFF, S ;

DISTECHE, CM ;

SIMONEAUX, DK ;

FANSLOW, WC ;

BELMONT, J ;

SPRIGGS, MK .

SCIENCE, 1993, 259 (5097) :990-993

[4] Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion [J].

Arakawa, H ;

Hauschild, J ;

Buerstedde, JM .

SCIENCE, 2002, 295 (5558) :1301-1306

[5]

Aravind L, 1999, In Silico Biol, V1, P69

[6] THE CD40 LIGAND, GP39, IS DEFECTIVE IN ACTIVATED T-CELLS FROM PATIENTS WITH X-LINKED HYPER-IGM SYNDROME [J].

ARUFFO, A ;

FARRINGTON, M ;

HOLLENBAUGH, D ;

LI, X ;

MILATOVICH, A ;

NONOYAMA, S ;

BAJORATH, J ;

GROSMAIRE, LS ;

STENKAMP, R ;

NEUBAUER, M ;

ROBERTS, RL ;

NOELLE, RJ ;

LEDBETTER, JA ;

FRANCKE, U ;

OCHS, HD .

CELL, 1993, 72 (02) :291-300

[7] Increased transcription levels induce higher mutation rates in a hypermutating cell line [J].

Bachl, J ;

Carlson, C ;

Gray-Schopfer, V ;

Dessing, M ;

Olsson, C .

JOURNAL OF IMMUNOLOGY, 2001, 166 (08) :5051-5057

[8] Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice [J].

Barnes, DE ;

Stamp, G ;

Rosewell, I ;

Denzel, A ;

Lindahl, T .

CURRENT BIOLOGY, 1998, 8 (25) :1395-1398

[9] The mechanism and regulation of chromosomal V(D)J recombination [J].

Bassing, CH ;

Swat, W ;

Alt, FW .

CELL, 2002, 109 :S45-S55

[10] Somatic hypermutation in the absence of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) or recombination-activating gene (RAG)1 activity [J].

Bemark, M ;

Sale, JE ;

Kim, HJ ;

Berek, C ;

Cosgrove, RA ;

Neuberger, MS .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (10) :1509-1514

← 1 2 3 4 5 6 7 8 9 10 →