Chromosomal position of a VH gene segment determines its activation and inactivation as a substrate for V(D)J recombination

被引：28

作者：

Bates, Jamie Geier ^{[1
]}

Cado, Dragana ^{[1
]}

Nolla, Hector ^{[1
]}

Schlissel, Mark S. ^{[1
]}

机构：

[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol, Berkeley, CA 94720 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2007年 / 204卷 / 13期

关键词：

D O I：

10.1084/jem.20071787

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Complete IgHC gene rearrangement occurs only in B cells in a stage-specific and ordered manner. We used gene targeting to reposition a distal V-H gene segment to a region just 5 ' of the D-H gene cluster and found its activation to be highly dependent on the chromosomal domain within which it resides. The targeted VH gene segment rearranged at a higher frequency than its endogenous counterpart, its rearrangement was no longer ordered, and its ability to be silenced by allelic exclusion was lost. Additionally, the targeted VH gene segment lost lineage specificity, as VDJ(H) rearrangement was observed in thymocytes. These data suggest that locus contraction, mimicked by proximal targeting, can override any regulation imposed by DNA sequences immediately surrounding VH gene segments.

引用

页码：3247 / 3256

页数：10

共 48 条

[1] Regulation of IgH gene assembly:: Role of the intronic enhancer and 5′DQ52 region in targeting DHJH recombination [J].

Afshar, R ;

Pierce, S ;

Bolland, DJ ;

Corcoran, A ;

Oltz, EM .

JOURNAL OF IMMUNOLOGY, 2006, 176 (04) :2439-2447

[2] COORDINATION OF IMMUNOGLOBULIN DJH TRANSCRIPTION AND D-TO-JH REARRANGEMENT BY PROMOTER-ENHANCER APPROXIMATION [J].

ALESSANDRINI, A ;

DESIDERIO, SV .

MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (04) :2096-2107

[3] ORDERED REARRANGEMENT OF IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION SEGMENTS [J].

ALT, FW ;

YANCOPOULOS, GD ;

BLACKWELL, TK ;

WOOD, C ;

THOMAS, E ;

BOSS, M ;

COFFMAN, R ;

ROSENBERG, N ;

TONEGAWA, S ;

BALTIMORE, D .

EMBO JOURNAL, 1984, 3 (06) :1209-1219

[4] Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5 [J].

Bertolino, E ;

Reddy, K ;

Medina, KL ;

Parganas, E ;

Ihle, J ;

Singh, H .

NATURE IMMUNOLOGY, 2005, 6 (08) :836-843

[5] Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer: The role of enhancer elements in controlling V(D)J recombination accessibility [J].

Bories, JC ;

Demengeot, J ;

Davidson, L ;

Alt, FW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :7871-7876

[6] Deletion of the mouse T-cell receptor beta gene enhancer blocks alpha beta T-cell development [J].

Bouvier, G ;

Watrin, F ;

Naspetti, M ;

Verthuy, C ;

Naquet, P ;

Ferrier, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :7877-7881

[7] IMMUNOGLOBULIN GENE REARRANGEMENT IN B-CELL DEFICIENT MICE GENERATED BY TARGETED DELETION OF THE J(H) LOCUS [J].

CHEN, JZ ;

TROUNSTINE, M ;

ALT, FW ;

YOUNG, F ;

KURAHARA, C ;

LORING, JF ;

HUSZAR, D .

INTERNATIONAL IMMUNOLOGY, 1993, 5 (06) :647-656

[8] MUTATIONS OF THE INTRONIC IGH ENHANCER AND ITS FLANKING SEQUENCES DIFFERENTIALLY AFFECT ACCESSIBILITY OF THE J(H)-LOCUS [J].

CHEN, JZ ;

YOUNG, F ;

BOTTARO, A ;

STEWART, V ;

SMITH, RK ;

ALT, FW .

EMBO JOURNAL, 1993, 12 (12) :4635-4645

[9] Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements [J].

Chowdhury, D ;

Sen, R .

IMMUNITY, 2003, 18 (02) :229-241

[10] Stepwise activation of the immunoglobulin μ heavy chain gene locus [J].

Chowdhury, D ;

Sen, R .

EMBO JOURNAL, 2001, 20 (22) :6394-6403

← 1 2 3 4 5 →