| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B Regulates Ig
Light Chain Gene Rearrangement1
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
The tissue- and stage-specific assembly of Ig and TCR genes is
mediated by a common V(D)J recombinase complex in precursor
lymphocytes. Directed alterations in the accessibility of V, D, and J
gene segments target the recombinase to specific Ag receptor
loci. Accessibility within a given locus is regulated by the functional
interaction of transcription factors with cognate enhancer elements and
correlates with the transcriptional activity of unrearranged gene
segments. As demonstrated in our prior studies, rearrangement of the
Ig
locus is regulated by the inducible transcription factor NF-B.
In contrast to the Ig locus, known transcriptional control elements
in the Ig
locus lack functional NF-B binding sites. Consistent
with this observation, the expression of assembled Ig genes in
mature B cells has been shown to be NF-B independent. Nonetheless,
we now show that specific repression of NF-B inhibits germline
transcription and recombination of Ig gene segments in precursor B
cells. Molecular analyses indicate that the block in NF-B impairs
Ig rearrangement at the level of recombinase accessibility. In
contrast, the activities of known Ig promoter and enhancer elements
are unaffected in the same cellular background. These findings expand
the range of NF-B action in precursor B cells beyond Ig to
include the control of recombinational accessibility at both L chain
loci. Moreover, our results strongly suggest the existence of a novel
Ig regulatory element that is either directly or indirectly
activated by NF-B during the early stages of B cell
development.
This article has been cited by other articles:
|
|
 |
|
  E. J. Cadera, F. Wan, R. H. Amin, H. Nolla, M. J. Lenardo, and M. S. Schlissel NF-{kappa}B activity marks cells engaged in receptor editing J. Exp. Med., August 3, 2009; 206(8): 1803 - 1816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Thomas, H. Miyashita, R. M. Cobb, S. Pierce, M. Tachibana, E. Hobeika, M. Reth, Y. Shinkai, and E. M. Oltz Functional Analysis of Histone Methyltransferase G9a in B and T Lymphocytes J. Immunol., July 1, 2008; 181(1): 485 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Souto-Carneiro, R. Fritsch, N. Sepulveda, M. J. Lagareiro, N. Morgado, N. S. Longo, and P. E. Lipsky The NF-{kappa}B Canonical Pathway Is Involved in the Control of the Exonucleolytic Processing of Coding Ends during V(D)J Recombination J. Immunol., January 15, 2008; 180(2): 1040 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Martone, G. Euskirchen, P. Bertone, S. Hartman, T. E. Royce, N. M. Luscombe, J. L. Rinn, F. K. Nelson, P. Miller, M. Gerstein, et al. Distribution of NF-{kappa}B-binding sites across human chromosome 22 PNAS, October 14, 2003; 100(21): 12247 - 12252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Cowell, M. Davila, K. Yang, T. B. Kepler, and G. Kelsoe Prospective Estimation of Recombination Signal Efficiency and Identification of Functional Cryptic Signals in the Genome by Statistical Modeling J. Exp. Med., January 20, 2003; 197(2): 207 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Sikes, A. Meade, R. Tripathi, M. S. Krangel, and E. M. Oltz Regulation of V(D)J recombination: A dominant role for promoter positioning in gene segment accessibility PNAS, September 17, 2002; 99(19): 12309 - 12314. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
