Antigen Receptor Engagement Turns off the V(D)J Recombination Machinery in Human Tonsil B Cells

Antigen Receptor Engagement Turns off the V(D)J Recombination Machinery in Human Tonsil B Cells 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. secondary V(D)J recombination germinal center recombination activating gene surrogate light chain terminal deoxynucleotidyl transferase Footnotes 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. Abbreviations used in this paper: GC germinal center FM follicular mantle ΨL surrogate light chain LM ligation-mediated RAG recombination activating gene RSS recombination signal sequences RT reverse transcriptase TdT terminal deoxynucleotidyl transferase Submitted: 29 May 1998 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

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Publisher
Rockefeller University Press
Copyright
© 1998 Rockefeller University Press
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.188.4.765
Publisher site
See Article on Publisher Site

Abstract

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. secondary V(D)J recombination germinal center recombination activating gene surrogate light chain terminal deoxynucleotidyl transferase Footnotes 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. Abbreviations used in this paper: GC germinal center FM follicular mantle ΨL surrogate light chain LM ligation-mediated RAG recombination activating gene RSS recombination signal sequences RT reverse transcriptase TdT terminal deoxynucleotidyl transferase Submitted: 29 May 1998

Journal

The Journal of Experimental MedicineRockefeller University Press

Published: Aug 17, 1998

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