The germinal center (GC) is an anatomic compartment found in peripheral lymphoid organs, wherein B cells undergo clonal expansion, somatic mutation, switch recombination, and reactivate immunoglobulin gene V(D)J recombination. As a result of somatic mutation, some GC B cells develop higher affinity antibodies, whereas others suffer mutations that decrease affinity, and still others may become self-reactive. It has been proposed that secondary V(D)J rearrangements in GCs might rescue B cells whose receptors are damaged by somatic mutations. Here we present evidence that mature human tonsil B cells coexpress conventional light chains and recombination associated genes, and that they extinguish recombination activating gene and terminal deoxynucleotidyl transferase expression when their receptors are cross-linked. Thus, the response of the recombinase to receptor engagement in peripheral B cells is the opposite of the response in developing B cells to the same stimulus. These observations suggest that receptor revision is a mechanism for receptor diversification that is turned off when antigen receptors are cross-linked by the cognate antigen.
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17 August 1998
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August 17 1998
Antigen Receptor Engagement Turns off the V(D)J Recombination Machinery in Human Tonsil B Cells
Eric Meffre,
Eric Meffre
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Fotini Papavasiliou,
Fotini Papavasiliou
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Paul Cohen,
Paul Cohen
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Odette de Bouteiller,
Odette de Bouteiller
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Diana Bell,
Diana Bell
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Hajime Karasuyama,
Hajime Karasuyama
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Claudine Schiff,
Claudine Schiff
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Jacques Banchereau,
Jacques Banchereau
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Yong-Jun Liu,
Yong-Jun Liu
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Michel C. Nussenzweig
Michel C. Nussenzweig
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
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Eric Meffre
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Fotini Papavasiliou
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Paul Cohen
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Odette de Bouteiller
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Diana Bell
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Hajime Karasuyama
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Claudine Schiff
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Jacques Banchereau
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Yong-Jun Liu
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Michel C. Nussenzweig
From the *Laboratory of Molecular Immunology and the ‡Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; §Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the ‖Baylor Institute for Immunology Research, Sammons Cancer Center, Dallas, Texas 75246; the ¶Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113, Japan; the **Centre d'Immunologie de Marseille-Luminy, 13288 Marseille cedex 09, France; and the ††DNAX Research Institute, Palo Alto, California 94304-1104
Address correspondence to Michel C. Nussenzweig, Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021. Phone: 212-327-8067; Fax: 212-327-8370; E-mail: [email protected]
E. Meffre was supported by a grant from the Philippe Foundation, and P. Cohen by National Institutes of Health (NIH) Medical Scientist Training Program grant GM-77039. This work was supported by grants from the NIH to M.C. Nussenzweig. M.C. Nussenzweig is an associate investigator of the Howard Hughes Medical Institute.
Received:
May 29 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (4): 765–772.
Article history
Received:
May 29 1998
Citation
Eric Meffre, Fotini Papavasiliou, Paul Cohen, Odette de Bouteiller, Diana Bell, Hajime Karasuyama, Claudine Schiff, Jacques Banchereau, Yong-Jun Liu, Michel C. Nussenzweig; Antigen Receptor Engagement Turns off the V(D)J Recombination Machinery in Human Tonsil B Cells . J Exp Med 17 August 1998; 188 (4): 765–772. doi: https://doi.org/10.1084/jem.188.4.765
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