Surrogate light chain expression is required to establish immunoglobulin heavy chain allelic exclusion during early B cell development

被引:136
作者
Loffert, D
Ehlich, A
Muller, W
Rajewsky, K
机构
[1] Institute for Genetics, University of Cologne, D-50931 Cologne
关键词
D O I
10.1016/S1074-7613(00)80678-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Allelic exclusion at the IgH locus was examined in B lineage cells of wild-type mice and mice unable to express the surrogate light chain molecule lambda 5 using a single-cell PCR approach. By analyzing B precursor cells containing two V(H)D(H)J(H) rearrangements, we found that in wild-type animals, cells are allelically excluded as soon as mu chains are expressed. Furthermore, we provide evidence that in cells expressing D mu proteins V-H-->D(H)J(H) rearrangement is inhibited. In contrast, in the absence of lambda 5 protein, B precursor cells were allelically ''included,'' indicating that allelic exclusion at the IgH locus requires expression of the pre-B cell receptor either containing a mu chain or a D mu chain. However, although mu chain double-producing B precursor cells are generated in lambda 5-deficient mice, such cells were not detected among surface immunoglobulin positive B cells.
引用
收藏
页码:133 / 144
页数:12
相关论文
共 77 条
[1]   ORGANIZATION AND REORGANIZATION OF IMMUNOGLOBULIN GENES IN A-MULV TRANSFORMED-CELLS - REARRANGEMENT OF HEAVY BUT NOT LIGHT CHAIN GENES [J].
ALT, F ;
ROSENBERG, N ;
LEWIS, S ;
THOMAS, E ;
BALTIMORE, D .
CELL, 1981, 27 (02) :381-390
[2]   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
[3]   JOINING OF IMMUNOGLOBULIN HEAVY-CHAIN GENE SEGMENTS - IMPLICATIONS FROM A CHROMOSOME WITH EVIDENCE OF 3 D-JH FUSIONS [J].
ALT, FW ;
BALTIMORE, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (13) :4118-4122
[4]  
BAUER SR, 1993, TRANSGENE, V1, P33
[5]   HEAVY-CHAIN VARIABLE REGION CONTRIBUTION TO THE NPB FAMILY OF ANTIBODIES - SOMATIC MUTATION EVIDENT IN A GAMMA-2A VARIABLE REGION [J].
BOTHWELL, ALM ;
PASKIND, M ;
RETH, M ;
IMANISHIKARI, T ;
RAJEWSKY, K ;
BALTIMORE, D .
CELL, 1981, 24 (03) :625-637
[6]  
CAMBIER JC, 1994, ANNU REV IMMUNOL, V12, P457, DOI 10.1146/annurev.immunol.12.1.457
[7]   ENUMERATION AND CHARACTERIZATION OF DJH STRUCTURES IN MOUSE FETAL LIVER [J].
CHANG, Y ;
PAIGE, CJ ;
WU, GE .
EMBO JOURNAL, 1992, 11 (05) :1891-1899
[8]   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
[9]   THE PROTECTON - THE UNIT OF HUMORAL IMMUNITY SELECTED BY EVOLUTION [J].
COHN, M ;
LANGMAN, RE .
IMMUNOLOGICAL REVIEWS, 1990, 115 :7-147
[10]   ABERRANT REARRANGEMENTS CONTRIBUTE SIGNIFICANTLY TO THE ALLELIC EXCLUSION OF IMMUNOGLOBULIN GENE-EXPRESSION [J].
COLECLOUGH, C ;
PERRY, RP ;
KARJALAINEN, K ;
WEIGERT, M .
NATURE, 1981, 290 (5805) :372-378