| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany;
Lilly GmbH, Bad Homburg, Germany;
Center for Genomics Research, Karolinska Institute, Stockholm, Sweden;
§
National Veterinary and Food Research Institute, Regional Laboratory of Kuopio, Kuopio, Finland; and
¶
Department of Clinical Microbiology, University of Kuopio, and Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland
The process of V(D)J recombination that leads to the assembly of Ig gene segments is tightly controlled during B cell differentiation. Two germline transcripts, one of which (µ0) originates from the promoter region of DQ52, may control the accessibility of the heavy chain locus. Here, we present the analysis of a mouse line in which the DQ52 gene together with its regulatory sequences is deleted by a Cre/loxP-based strategy. In F1 (DQ52+/-) mice, the use of the JH3 and JH4 elements in DJ or VDJ junctions of the DQ52- allele was strongly reduced in both the bone marrow pre-B and spleen cells, while the JH1 and JH2 elements were used with normal frequencies. In addition, IgM+ B cells of bone marrow and spleen used the DQ52- allele less frequently. On DJ joints of the DQ52- allele, there was 2 times less processing of JH3 ends, which resulted in clearly increased addition of P nucleotides. Although the use of D elements in DJ joints was quite similar, an altered D repertoire was found in VDJ joints of the DQ52- allele. In splenic B cells of the DQ52-/- mouse the amino acid distribution of the CDR3 was skewed, probably to compensate for the altered processing of JH3 ends. Thus, we have shown an interesting selective effect of the DQ52 region on controlling accessibility to 3' JH elements on the Ig locus, which also seems to influence the processing of DJ joints. We propose a model in which the DQ52 promoter region enhances the induction of secondary DJ rearrangements.
This article has been cited by other articles:
|
|
 |
|
  M. Zemlin, R. L. Schelonka, G. C. Ippolito, C. Zemlin, Y. Zhuang, G. L. Gartland, L. Nitschke, J. Pelkonen, K. Rajewsky, and H. W. Schroeder Jr. Regulation of Repertoire Development through Genetic Control of DH Reading Frame Preference J. Immunol., December 15, 2008; 181(12): 8416 - 8424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Bates, D. Cado, H. Nolla, and M. S. Schlissel Chromosomal position of a VH gene segment determines its activation and inactivation as a substrate for V(D)J recombination J. Exp. Med., December 24, 2007; 204(13): 3247 - 3256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Retter, C. Chevillard, M. Scharfe, A. Conrad, M. Hafner, T.-H. Im, M. Ludewig, G. Nordsiek, S. Severitt, S. Thies, et al. Sequence and Characterization of the Ig Heavy Chain Constant and Partial Variable Region of the Mouse Strain 129S1 J. Immunol., August 15, 2007; 179(4): 2419 - 2427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Ippolito, R. L. Schelonka, M. Zemlin, I. I. Ivanov, R. Kobayashi, C. Zemlin, G. L. Gartland, L. Nitschke, J. Pelkonen, K. Fujihashi, et al. Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production J. Exp. Med., June 12, 2006; 203(6): 1567 - 1578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Pawlitzky, C. V. Angeles, A. M. Siegel, M. L. Stanton, R. Riblet, and P. H. Brodeur Identification of a Candidate Regulatory Element within the 5' Flanking Region of the Mouse Igh Locus Defined by Pro-B Cell-Specific Hypersensitivity Associated with Binding of PU.1, Pax5, and E2A. J. Immunol., June 1, 2006; 176(11): 6839 - 6851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L Cassady-Cain and A. K Kaushik Increased negative selection impairs neonatal B cell repertoire but does not directly lead to generation of disease-associated IgM auto-antibodies Int. Immunol., May 1, 2006; 18(5): 661 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Maes, S. Chappaz, P. Cavelier, L. O'Neill, B. Turner, F. Rougeon, and M. Goodhardt Activation of V(D)J Recombination at the IgH Chain JH Locus Occurs within a 6-Kilobase Chromatin Domain and Is Associated with Nucleosomal Remodeling J. Immunol., May 1, 2006; 176(9): 5409 - 5417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Afshar, S. Pierce, D. J. Bolland, A. Corcoran, and E. M. Oltz Regulation of IgH Gene Assembly: Role of the Intronic Enhancer and 5'DQ52 Region in Targeting DHJH Recombination J. Immunol., February 15, 2006; 176(4): 2439 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Schelonka, I. I. Ivanov, D. H. Jung, G. C. Ippolito, L. Nitschke, Y. Zhuang, G. L. Gartland, J. Pelkonen, F. W. Alt, K. Rajewsky, et al. A Single DH Gene Segment Creates Its Own Unique CDR-H3 Repertoire and Is Sufficient for B cell Development and Immune Function J. Immunol., November 15, 2005; 175(10): 6624 - 6632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Kalmanovich and R. Mehr Models for Antigen Receptor Gene Rearrangement. III. Heavy and Light Chain Allelic Exclusion J. Immunol., January 1, 2003; 170(1): 182 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Delpy, C. Decourt, M. Le Bert, and M. Cogne B Cell Development Arrest Upon Insertion of a neo Gene Between JH and E{micro}: Promoter Competition Results in Transcriptional Silencing of Germline JH and Complete V(D)J Rearrangements J. Immunol., December 15, 2002; 169(12): 6875 - 6882. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
