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Science 20 December 1996:
Vol. 274. no. 5295, pp. 2094 - 2097
DOI: 10.1126/science.274.5295.2094
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Reports

Neoteny in Lymphocytes: Rag1 and Rag2 Expression in Germinal Center B Cells

Shuhua Han, Biao Zheng, David G. Schatz, Eugenia Spanopoulou, Garnett Kelsoe *

The products of the Rag1 and Rag2 genes drive genomic V(D)J rearrangements that assemble functional immunoglobulin and T cell antigen receptor genes. Expression of the Rag genes has been thought to be limited to developmentally immature lymphocyte populations that in normal adult animals are primarily restricted to the bone marrow and thymus. Abundant RAG1 and RAG2 protein and messenger RNA was detected in the activated B cells that populate murine splenic and Peyer's patch germinal centers. Germinal center B cells thus share fundamental characteristics of immature lymphocytes, raising the possibility that antigen-dependent secondary V(D)J rearrangements modify the peripheral antibody repertoire.

S. Han, B. Zheng, G. Kelsoe, Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
D. G. Schatz, Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
E. Spanopoulou, Mount Sinai Cancer Center, New York, NY 10021, USA.
*   To whom correspondence should be addressed.


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Follicular lymphomas' BCL-2/IgH junctions contain templated nucleotide insertions: novel insights into the mechanism of t(14;18) translocation.
U. Jager, S. Bocskor, T. Le, G. Mitterbauer, I. Bolz, A. Chott, M. Kneba, C. Mannhalter, and B. Nadel (2000)
Blood 95, 3520-3529
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Humoral Immune Responses in Cr2-/- Mice: Enhanced Affinity Maturation but Impaired Antibody Persistence.
Z. Chen, S. B. Koralov, M. Gendelman, M. C. Carroll, and G. Kelsoe (2000)
J. Immunol. 164, 4522-4532
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Cutting Edge: Recombinase-Activating Gene Expression and V(D)J Recombination in CD4+CD3low Mature T Lymphocytes.
E. Lantelme, B. Palermo, L. Granziero, S. Mantovani, R. Campanelli, V. Monafo, A. Lanzavecchia, and C. Giachino (2000)
J. Immunol. 164, 3455-3459
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A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication.
K. Kuwahara, M. Yoshida, E. Kondo, A. Sakata, Y. Watanabe, E. Abe, Y. Kouno, S. Tomiyasu, S. Fujimura, T. Tokuhisa, et al. (2000)
Blood 95, 2321-2328
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Cutting Edge: Absence of Expression of RAG1 in Peritoneal B-1 Cells Detected by Knocking into RAG1 Locus with Green Fluorescent Protein Gene.
N. Kuwata, H. Igarashi, T. Ohmura, S. Aizawa, and N. Sakaguchi (1999)
J. Immunol. 163, 6355-6359
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Regulated Genomic Instability and Neoplasia in the Lymphoid Lineage.
G. J. Vanasse, P. Concannon, and D. M. Willerford (1999)
Blood 94, 3997-4010
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Distinct Signal Thresholds for the Unique Antigen Receptor-Linked Gene Expression Programs in Mature and Immature B Cells.
R. J. Benschop, D. Melamed, D. Nemazee, and J. C. Cambier (1999)
J. Exp. Med. 190, 749-756
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B Lymphocyte Selection and Age-Related Changes in VH Gene Usage in Mutant Alicia Rabbits.
X. Zhu, A. Boonthum, S.-K. Zhai, and K. L. Knight (1999)
J. Immunol. 163, 3313-3320
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Somatic Mutation and Light Chain Rearrangement Generate Autoimmunity in Anti-Single-Stranded DNA Transgenic Mrl/lpr Mice.
F. Brard, M. Shannon, E. L. Prak, S. Litwin, and M. Weigert (1999)
J. Exp. Med. 190, 691-704
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An inverse relationship between T cell receptor affinity and antigen dose during CD4+ T cell responses in vivo and in vitro.
W. Rees, J. Bender, T. K. Teague, R. M. Kedl, F. Crawford, P. Marrack, and J. Kappler (1999)
PNAS 96, 9781-9786
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Antigen-Induced Somatic Diversification of Rabbit IgH Genes: Gene Conversion and Point Mutation.
C. R. Winstead, S.-K. Zhai, P. Sethupathi, and K. L. Knight (1999)
J. Immunol. 162, 6602-6612
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Distinct Factors Regulate the Murine RAG-2 Promoter in B- and T-Cell Lines.
J. Lauring and M. S. Schlissel (1999)
Mol. Cell. Biol. 19, 2601-2612
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Gene Conversion and Hypermutation During Diversification of VH Sequences in Developing Splenic Germinal Centers of Immunized Rabbits.
E. Schiaffella, D. Sehgal, A. O. Anderson, and R. G. Mage (1999)
J. Immunol. 162, 3984-3995
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Activated Ras Signals Developmental Progression of Recombinase-activating Gene (RAG)-deficient Pro-B Lymphocytes.
A. C. Shaw, W. Swat, R. Ferrini, L. Davidson, and F. W. Alt (1999)
J. Exp. Med. 189, 123-129
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RAG Expression in B Cells in Secondary Lymphoid Tissues.
W. YU, H. NAGAOKA, Z. MISULOVIN, E. MEFFRE, H. SUH, M. JANKOVIC, N. YANNOUTSOS, R. CASELLAS, E. BESMER, F. PAPAVASILIOU, et al. (1999)
Cold Spring Harb Symp Quant Biol 64, 207-210
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Analyses of Single B Cells by Polymerase Chain Reaction Reveal Rearranged VH with Germline Sequences in Spleens of Immunized Adult Rabbits: Implications for B Cell Repertoire Maintenance and Renewal.
D. Sehgal, E. Schiaffella, A. O. Anderson, and R. G. Mage (1998)
J. Immunol. 161, 5347-5356
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Rapid elimination of mature autoreactive B cells demonstrated by Cre-induced change in B cell antigen receptor specificity in vivo.
K.-P. Lam and K. Rajewsky (1998)
PNAS 95, 13171-13175
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Antigen Receptor Engagement Turns off the V(D)J Recombination Machinery in Human Tonsil B Cells.
E. Meffre, F. Papavasiliou, P. Cohen, O. de Bouteiller, D. Bell, H. Karasuyama, C. Schiff, J. Banchereau, Y.-J. Liu, and M. C. Nussenzweig (1998)
J. Exp. Med. 188, 765-772
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Surrogate Light Chain Production During B Cell Differentiation: Differential Intracellular Versus Cell Surface Expression.
Y.-H. Wang, J. Nomura, O. M. Faye-Petersen, and M. D. Cooper (1998)
J. Immunol. 161, 1132-1139
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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.
M. Hikida, Y. Nakayama, Y. Yamashita, Y. Kumazawa, S.-I. Nishikawa, and H. Ohmori (1998)
J. Exp. Med. 188, 365-372
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Restricted Expression of E2A Protein in Primary Human Tissues Correlates with Proliferation and Differentiation.
M. N. Rutherford and D. P. LeBrun (1998)
Am. J. Pathol. 153, 165-173
   Abstract »    Full Text »    PDF »
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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Kinetics of Establishing the Memory B Cell Population as Revealed by CD38 Expression.
A. Ridderstad and D. M. Tarlinton (1998)
J. Immunol. 160, 4688-4695
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Oligoclonal Development of B Cells Bearing Discrete Ig Chains in Chicken Single Germinal Centers.
H. Arakawa, K.-i. Kuma, M. Yasuda, S. Furusawa, S. Ekino, and H. Yamagishi (1998)
J. Immunol. 160, 4232-4241
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The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, C{micro}-C{delta} 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
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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
   Abstract »    Full Text »    PDF »
V(D)J Recombinase Activity in a Subset of Germinal Center B Lymphocytes.
S. Han, S. R. Dillon, B. Zheng, M. Shimoda, M. S. Schlissel, and G. Kelsoe (1997)
Science 278, 301-305
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