E2A expression stimulates Ig Hypermutation

被引：52

作者：

Schoetz, Ulrike ^{[1
]}

Cervelli, Manuela ^{[1
]}

Wang, Yan-Dong ^{[1
]}

Fiedler, Petra ^{[1
]}

Buerstedde, Jean-Marie ^{[1
]}

机构：

[1] GSF, Natl Res Ctr Environm & Hlth, Inst Mol Radiobiol, D-85764 Neuherberg, Germany

来源：

JOURNAL OF IMMUNOLOGY | 2006年 / 177卷 / 01期

关键词：

D O I：

10.4049/jimmunol.177.1.395

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Ig hypermutation is limited to a region of similar to 2 kb downstream of the transcription start sites of the Ig loci. The process requires transcription and the presence of Ig enhancer sequences, and is initiated by the activation-induced cytidine deaminase (AID)mediated deamination of cytidine bases. It remains unknown why AID causes mutations selectively in the Ig genes and not in most other transcribed loci of B cells. In this study, we report that the inactivation of the E2A gene strongly reduces the rate of Ig L chain mutations in the chicken B cell line DT40 without affecting the levels of surface Ig or AID expression. The defect is complemented by the expression of cDNAs corresponding to either of the two E2A splice variants E12 or E47. The results suggest that E2A-encoded proteins enhance Ig hypermutation by recruitment of AID to the Ig loci.

引用

页码：395 / 400

页数：6

共 24 条

[1] An explicit representation of the Luria-Delbruck distribution [J].

Angerer, WP .

JOURNAL OF MATHEMATICAL BIOLOGY, 2001, 42 (02) :145-174

[2] Activation-induced cytidine deaminase initiates immunoglobulin gene conversion and hypermutation by a common intermediate [J].

Arakawa, H ;

Saribasak, H ;

Buerstedde, JM .

PLOS BIOLOGY, 2004, 2 (07) :967-974

[3] Mutants IoxP vectors for selectable marker recycle and conditional knock-outs [J].

Arakawa H. ;

Lodygin D. ;

Buerstedde J.-M. .

BMC Biotechnology, 1 (1)

[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] ELEMENTS REGULATING SOMATIC HYPERMUTATION OF AN IMMUNOGLOBULIN-KAPPA GENE - CRITICAL ROLE FOR THE INTRON ENHANCER MATRIX ATTACHMENT REGION [J].

BETZ, AG ;

MILSTEIN, C ;

GONZALEZFERNANDEZ, A ;

PANNELL, R ;

LARSON, T ;

NEUBERGER, MS .

CELL, 1994, 77 (02) :239-248

[6] Full-length cDNAs from chicken bursal lymphocytes to facilitate gene function analysis [J].

Randolph B Caldwell ;

Andrzej M Kierzek ;

Hiroshi Arakawa ;

Yuri Bezzubov ;

Jolanta Zaim ;

Petra Fiedler ;

Stefan Kutter ;

Artem Blagodatski ;

Diyana Kostovska ;

Marek Koter ;

Jiri Plachy ;

Piero Carninci ;

Yoshihide Hayashizaki ;

Jean-Marie Buerstedde .

Genome Biology, 6 (1)

[7] The chicken Ig light chain 3′-enhancer is essential for gene expression and regulates gene conversion via the transcription factor E2A [J].

Conlon, TM ;

Meyer, KB .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2006, 36 (01) :139-148

[8]

CONLON TM, 2000, BMC IMMUNOL, V14, P5

[9] Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase [J].

Di Noia, J ;

Neuberger, MS .

NATURE, 2002, 419 (6902) :43-48

[10]

Gordon P, 2003, PLOUGHSHARES, V29, P79

← 1 2 3 →