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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 dagger

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 kappa  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.

dagger    To whom correspondence should be addressed. E-mail: gkelsoe{at}umabnet.ab.umd.edu

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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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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)
J. Exp. Med. 187, 1169-1178
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »


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