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J. Exp. Med., Volume 188, Number 4, August 17, 1998 765-772

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

By Eric Meffre,*Dagger Fotini Papavasiliou,* Paul Cohen,* Odette de Bouteiller,§ Diana Bell,parallel Hajime Karasuyama, Claudine Schiff,** Jacques Banchereau,parallel Yong-Jun Liu,Dagger Dagger and Michel C. Nussenzweig*Dagger

From the * Laboratory of Molecular Immunology and the Dagger  Howard Hughes Medical Institute, The Rockefeller University, New York 10021-6399; § Schering-Plough Laboratory for Immunobiology, Dardilly 69571, France; the parallel  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 Dagger Dagger  DNAX Research Institute, Palo Alto, California 94304-1104

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.

Key words: secondary V(D)J recombinationgerminal centerrecombination activating genesurrogate light chainterminal deoxynucleotidyl transferase


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