scholarly journals Cux/CDP Homeoprotein Is a Component of NF-μNR and Represses the Immunoglobulin Heavy Chain Intronic Enhancer by Antagonizing the Bright Transcription Activator

1999 ◽  
Vol 19 (1) ◽  
pp. 284-295 ◽  
Author(s):  
Zhiyong Wang ◽  
Adrian Goldstein ◽  
Rui-Ting Zong ◽  
Danjun Lin ◽  
Ellis J. Neufeld ◽  
...  
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Nuclear Matrix ◽  
Binding Sites ◽  
Immunoglobulin Heavy Chain ◽  
Negative Regulator ◽  
Homeodomain Protein ◽  
Transcription Activator ◽  
Expression Library ◽  
Intronic Enhancer

ABSTRACT Nuclear matrix attachment regions (MARs) flanking the immunoglobulin heavy chain intronic enhancer (Eμ) are the targets of the negative regulator, NF-μNR, found in non-B and early pre-B cells. Expression library screening with NF-μNR binding sites yielded a cDNA clone encoding an alternatively spliced form of the Cux/CDP homeodomain protein. Cux/CDP fulfills criteria required for NF-μNR identity. It is expressed in non-B and early pre-B cells but not mature B cells. It binds to NF-μNR binding sites within Eμ with appropriate differential affinities. Antiserum specific for Cux/CDP recognizes a polypeptide of the predicted size in affinity-purified NF-μNR preparations and binds NF-μNR complexed with DNA. Cotransfection with Cux/CDP represses the activity of Eμ via the MAR sequences in both B and non-B cells. Cux/CDP antagonizes the effects of the Bright transcription activator at both the DNA binding and functional levels. We propose that Cux/CDP regulates cell-type-restricted, differentiation stage-specific Eμ enhancer activity by interfering with the function of nuclear matrix-bound transcription activators.

scholarly journals The absence of the transcription activator TFE3 impairs activation of B cells in vivo.

1997 ◽  
Vol 17 (6) ◽  
pp. 3335-3344 ◽  
Author(s):  
K Merrell ◽  
S Wells ◽  
A Henderson ◽  
J Gorman ◽  
F Alt ◽  
...  
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Cell Activation ◽  
Es Cells ◽  
Embryonic Stem ◽  
Transcription Activator ◽  
Intronic Enhancer ◽  
Heat Stable Antigen

TFE3 is a ubiquitously expressed member of the TFE3/mi family of basic helix loop helix zipper transcription factors. TFE3 binds to muE3 sites located in the immunoglobulin heavy-chain (IgH) intronic enhancer, heavy-chain variable region promoters, the Ig kappa intronic enhancer, and regulatory sites in other genes. To understand the role of TFE3 in Ig expression and lymphoid development, we used embryonic stem (ES) cell-mediated gene targeting and RAG2-/- blastocyst complementation to generate mice which lack TFE3 in their B and T lymphocytes. TFE3- ES cells fully reconstitute the B- and T-cell compartments, giving rise to normal patterns of IgM+ B220+ B cells and CD4+ and CD8+ T cells. However, TFE3- B cells show several defects consistent with poor B-cell activation. Serum IgM levels are reduced twofold and IgG and IgA isotypes are reduced three- to sixfold in the TFE3- chimeras even though in vitro, the TFE3- splenocytes secrete normal levels of all isotypes in response to lipopolysaccharide activation. Peripheral TFE3- B cells also show reduced surface expression of CD23 and CD24 (heat-stable antigen).

scholarly journals The HoxC4 Homeodomain Protein Mediates Activation of the Immunoglobulin Heavy Chain 3′ hs1,2 Enhancer in Human B Cells

2004 ◽  
Vol 279 (40) ◽  
pp. 42258-42269 ◽  
Author(s):  
Edmund C. Kim ◽  
Christopher R. Edmonston ◽  
Xiaoping Wu ◽  
András Schaffer ◽  
Paolo Casali
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Immunoglobulin Heavy Chain ◽  
Homeodomain Protein ◽  
Human B Cells

scholarly journals Critical roles of the immunoglobulin intronic enhancers in maintaining the sequential rearrangement of IgH and Igk loci

2006 ◽  
Vol 203 (7) ◽  
pp. 1721-1732 ◽  
Author(s):  
Matthew A. Inlay ◽  
Tongxiang Lin ◽  
Heather H. Gao ◽  
Yang Xu
Keyword(s):  
B Cells ◽  
Developmental Stage ◽  
Heavy Chain ◽  
Light Chain ◽  
Matrix Attachment Region ◽  
Cis Elements ◽  
Wild Type ◽  
Intronic Enhancer ◽  
Attachment Region

V(D)J recombination of immunoglobulin (Ig) heavy (IgH) and light chain genes occurs sequentially in the pro– and pre–B cells. To identify cis-elements that dictate this order of rearrangement, we replaced the endogenous matrix attachment region/Igk intronic enhancer (MiEκ) with its heavy chain counterpart (Eμ) in mice. This replacement, denoted EμR, substantially increases the accessibility of both Vκ and Jκ loci to V(D)J recombinase in pro–B cells and induces Igk rearrangement in these cells. However, EμR does not support Igk rearrangement in pre–B cells. Similar to that in MiEκ−/− pre–B cells, the accessibility of Vκ segments to V(D)J recombinase is considerably reduced in EμR pre–B cells when compared with wild-type pre–B cells. Therefore, Eμ and MiEκ play developmental stage-specific roles in maintaining the sequential rearrangement of IgH and Igk loci by promoting the accessibility of V, D, and J loci to the V(D)J recombinase.

The diversity of rearranged immunoglobulin heavy chain variable region genes in peripheral blood B cells of preterm infants is restricted by short third complementarity-determining regions but not by limited gene segment usage

Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1511-1513 ◽  
Author(s):  
Michael Zemlin ◽  
Karl Bauer ◽  
Michael Hummel ◽  
Sabine Pfeiffer ◽  
Simone Devers ◽  
...  
Keyword(s):  
B Cells ◽  
Preterm Infants ◽  
Heavy Chain ◽  
Peripheral Blood ◽  
Gene Segment ◽  
Immunoglobulin Heavy Chain ◽  
Term Infants ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Complementarity Determining Regions

The immunoglobulin diversity is restricted in fetal liver B cells. This study examined whether peripheral blood B cells of extremely preterm infants show similar restrictions (overrepresentation of some gene segments, short third complementarity-determining regions [CDR3]). DNA of rearranged immunoglobulin heavy chain genes was amplified by polymerase chain reaction, cloned, and sequenced. A total of 417 sequences were analyzed from 6 preterm infants (25-28 weeks of gestation), 6 term infants, and 6 adults. Gene segments from the entire VHand DH gene locus were rearranged in preterm infants, even though the DH7-27 segment was overrepresented (17% of rearrangements) compared to term infants (7%) and adults (2%). CDR3 was shorter in preterm infants (40 ± 10 nucleotides) than in term infants (44 ± 12) and adults (48 ± 14) (P < .001) due to shorter N regions. Somatic mutations were exclusively found in term neonates and adults (mutational frequency 0.8% and 1.8%). We conclude that preterm infants have no limitations in gene segment usage, whereas the diversity of CDR3 is restricted throughout gestation.

scholarly journals Changes in Locus-specific V(D)J Recombinase Activity Induced by Immunoglobulin Gene Products during B Cell Development

1997 ◽  
Vol 185 (4) ◽  
pp. 609-620 ◽  
Author(s):  
Andrei Constantinescu ◽  
Mark S. Schlissel
Keyword(s):  
B Cells ◽  
B Cell ◽  
Heavy Chain ◽  
Light Chain ◽  
Immunoglobulin Heavy Chain ◽  
Cell Development ◽  
B Cell Development ◽  
Allelic Exclusion ◽  
Chain Locus ◽  
Heavy Chain Locus

The process of V(D)J recombination is crucial for regulating the development of B cells and for determining their eventual antigen specificity. Here we assess the developmental regulation of the V(D)J recombinase directly, by monitoring the double-stranded DNA breaks produced in the process of V(D)J recombination. This analysis provides a measure of recombinase activity at immunoglobulin heavy and light chain loci across defined developmental stages spanning the process of B cell development. We find that expression of a complete immunoglobulin heavy chain protein is accompanied by a drastic change in the targeting of V(D)J recombinase activity, from being predominantly active at the heavy chain locus in pro-B cells to being exclusively restricted to the light chain loci in pre-B cells. This switch in locus-specific recombinase activity results in allelic exclusion at the immunoglobulin heavy chain locus. Allelic exclusion is maintained by a different mechanism at the light chain locus. We find that immature, but not mature, B cells that already express a functional light chain protein can undergo continued light chain gene rearrangement, by replacement of the original rearrangement on the same allele. Finally, we find that the developmentally regulated targeting of V(D)J recombination is unaffected by enforced rapid transit through the cell cycle induced by an Eμ-myc transgene.

scholarly journals The immunoglobulin heavy chain VH6-1 promoter regulates Ig transcription in non-B cells

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Lina Wu ◽  
Yang Liu ◽  
Xiaohui Zhu ◽  
Li Zhang ◽  
Jinfeng Chen ◽  
...  
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Immunoglobulin Heavy Chain
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