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Eric Meffre^*,, Fotini Papavasiliou^*, Paul Cohen^*, Odette de Bouteiller, Diana Bell^||, Hajime Karasuyama^¶, Claudine Schiff^**, Jacques Banchereau^||, Yong-Jun Liu, and 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

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 recombination • germinal center • recombination activating gene • surrogate light chain • terminal deoxynucleotidyl transferase

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: GC, germinal center; FM, follicular mantle; L, surrogate light chain; LM, ligation-mediated; RAG, recombination activating gene; RSS, recombination signal sequences; RT, reverse transcriptase; TdT, terminal deoxynucleotidyl transferase.

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