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Science 10 October 1997: Vol. 278. no. 5336, pp. 301 - 305 DOI: 10.1126/science.278.5336.301
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Reports
V(D)J Recombinase Activity in a Subset of Germinal Center B Lymphocytes
Shuhua Han,
*
Stacey R. Dillon,
*
Biao Zheng,
Michiko Shimoda,
Mark S. Schlissel,
Garnett Kelsoe
Reexpression of the V(D)J recombinase-activating genes
RAG1 and RAG2 in germinal center B cells creates
the potential for immunoglobulin gene rearrangement and the generation
of new antigen receptor specificities. Intermediate products of V(D)J
recombination are abundant in a subset of germinal center B cells,
demonstrating that the immunoglobulin light-chain locus becomes a
substrate for renewed V(D)J recombinase activity. This
recombinationally active cell compartment contains many heavy-chain VDJ
rearrangements that encode low-affinity or nonfunctional antibody. In
germinal centers, secondary V(D)J recombination may be induced by
diminished binding to antigen ligands, thereby limiting abrupt changes
in receptor specificity to B cells that are usually eliminated from the
germinal center reaction. This restriction preserves efficient antigen-driven selection in germinal centers while allowing for saltations in the somatic evolution of B cells.
S. Han, B. Zheng, M. Shimoda, G. Kelsoe, Department of
Microbiology and Immunology and Program in Molecular and Cell Biology,
University of Maryland School of Medicine, 655 West Baltimore Street,
Baltimore, MD 21201, USA.
S. R. Dillon and M. S. Schlissel, Departments of Medicine,
Molecular Biology and Genetics, and Oncology, The Johns Hopkins
University School of Medicine, Baltimore, MD 21205, USA.
*
These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail:
gkelsoe{at}umabnet.ab.umd.edu
Read the Full Text
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- Expression of Recombination Activating Genes in Germinal Center B Cells: Involvement of Interleukin 7 (IL-7) and the IL-7 Receptor.
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J. Exp. Med.
188, 365-372
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- Ku70 Is Required for Late B Cell Development and Immunoglobulin Heavy Chain Class Switching.
- J. P. Manis, Y. Gu, R. Lansford, E. Sonoda, R. Ferrini, L. Davidson, K. Rajewsky, and F. W. Alt (1998)
J. Exp. Med.
187, 2081-2089
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- Frequent Dysregulation of the c-maf Proto-Oncogene at 16q23 by Translocation to an Ig Locus in Multiple Myeloma.
- M. Chesi, P. L. Bergsagel, O. O. Shonukan, M. L. Martelli, L. A. Brents, T. Chen, E. Schrock, T. Ried, and W. M. Kuehl (1998)
Blood
91, 4457-4463
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- The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, Cµ-Cdelta Switch, and lambda Light Chain Expression.
- C. Arpin, O. de Bouteiller, D. Razanajaona, I. Fugier-Vivier, F. Briere, J. Banchereau, S. Lebecque, and Y.-J. Liu (1998)
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187, 1169-1178
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- Frequent occurrence of deletions and duplications during somatic hypermutation: Implications for oncogene translocations and heavy chain disease.
- T. Goossens, U. Klein, and R. Kuppers (1998)
PNAS
95, 2463-2468
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- Rearrangement of lambda Light Chain Genes in Mature B Cells In Vitro and In Vivo. Function of Reexpressed Recombination-activating Gene (RAG) Products.
- M. Hikida and H. Ohmori (1998)
J. Exp. Med.
187, 795-799
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