Variegated transcriptional activation of the immunoglobulin κ locus in pre-B cells contributes to the allelic exclusion of light-chain expression

被引：69

作者：

Liang, HE ^{[1
]}

Hsu, LY ^{[1
]}

Cado, D ^{[1
]}

Schlissel, MS ^{[1
]}

机构：

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

来源：

CELL | 2004年 / 118卷 / 01期

关键词：

D O I：

10.1016/j.cell.2004.06.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Regulated gene rearrangement is thought to underlie allelic exclusion, the observation that an individual B cell expresses only a single immunoglobulin molecule. Previous data has implicated transcriptional activation of rearranging loci in the regulation of their accessibility to the V(D)J recombinase. Using homologous recombination in ES cells, we have generated "knockin" mice which express a GFP cDNA from an unrearranged immunoglobulin kappa light-chain allele. Surprisingly, we find that only a small fraction of kappa alleles are highly transcribed in a population of pre-B cells, that such transcription is monoallelic, and that these highly transcribed alleles account for the vast majority of kappa light-chain gene rearrangement. These data lead us to suggest that probabilistic enhancer activation and allelic competition are part of the mechanism of kappa locus allelic exclusion and may be a general mechanism contributing to cellular differentiation during development.

引用

页码：19 / 29

页数：11

共 29 条

[11] PREFERENTIAL REARRANGEMENT OF THE IMMUNOGLOBULIN KAPPA-CHAIN JOINING REGION J-KAPPA-1 AND J-KAPPA-2 SEGMENTS IN MOUSE SPLEEN DNA [J].

NISHI, M ;

KATAOKA, T ;

HONJO, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (19) :6399-6403

[12]

Osmond D G, 1990, Semin Immunol, V2, P173

[13] A prematurely expressed Ig kappa transgene, but not a V kappa J kappa gene segment targeted into the Ig kappa locus, can rescue B cell development in lambda 5-deficient mice [J].

Pelanda, R ;

Schaal, S ;

Torres, RM ;

Rajewsky, K .

IMMUNITY, 1996, 5 (03) :229-239

[14] TRANSCRIPTION OF MOUSE KAPPA-CHAIN GENES - IMPLICATIONS FOR ALLELIC EXCLUSION [J].

PERRY, RP ;

KELLEY, DE ;

COLECLOUGH, C ;

SEIDMAN, JG ;

LEDER, P ;

TONEGAWA, S ;

MATTHYSSENS, G ;

WEIGERT, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (04) :1937-1941

[15] Regulating antigen-receptor gene assembly [J].

Schlissel, MS .

NATURE REVIEWS IMMUNOLOGY, 2003, 3 (11) :890-899

[16]

SCHLISSEL MS, 1994, J IMMUNOL, V153, P1645

[17] ACTIVATION OF IMMUNOGLOBULIN KAPPA GENE REARRANGEMENT CORRELATES WITH INDUCTION OF GERMLINE KAPPA GENE-TRANSCRIPTION [J].

SCHLISSEL, MS ;

BALTIMORE, D .

CELL, 1989, 58 (05) :1001-1007

[18] Structure of nonhairpin coding-end DNA breaks in cells undergoing V(D)J recombination [J].

Schlissel, MS .

MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (04) :2029-2037

[19] In vivo occupancy of the kappa light chain enhancers in primary pro- and pre-B cells: A model for kappa locus activation [J].

Shaffer, AL ;

Peng, A ;

Schlissel, MS .

IMMUNITY, 1997, 6 (02) :131-143

[20] Gene switching and the stability of odorant receptor gene choice [J].

Shykind, BM ;

Rohani, SC ;

O'Donnell, S ;

Nemes, A ;

Mendelsohn, M ;

Sun, YH ;

Axel, R ;

Barnea, G .

CELL, 2004, 117 (06) :801-815

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