The Journal of Experimental Medicine
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Published online 16 October 2006 doi:10.1084/jem.20061292
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 11, 2425-2431
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BRIEF DEFINITIVE REPORT

 Follicular lymphoma-like B cells in healthy individuals: a novel intermediate step in early lymphomagenesis

Sandrine Roulland1,2,3, Jean-Marc Navarro1,2,3, Pierre Grenot1,2,3, Michèle Milili1,2,3, Julie Agopian1,2,3, Bertrand Montpellier1,2,3, Pascal Gauduchon4, Pierre Lebailly4,5, Claudine Schiff1,2,3, and Bertrand Nadel1,2,3

1 Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, 13288 Marseille, France
2 Institut National de la Santé et de la Recherche Médicale (INSERM), U631, 13288 Marseille, France
3 Centre National de la Recherche Scientifique (CNRS), UMR6102, 13288 Marseille, France
4 Groupe Régional d'Etudes sur le Cancer EA1772, Université de Caen Basse-Normandie, CLCC François BACLESSE, 14076 Caen, France
5 Registre général des tumeurs du Calvados, CLCC François BACLESSE, 14076 Caen, France

CORRESPONDENCE Bertrand Nadel: nadel{at}ciml.univ-mrs.fr

Follicular lymphoma is one of the most common adult lymphoma, and remains virtually incurable despite its relatively indolent nature. t(14;18)(q32;q21) translocation, the genetic hallmark and early initiating event of follicular lymphoma (FL) pathogenesis, is also present at low frequency in the peripheral blood of healthy individuals. It has long been assumed that in healthy individuals t(14;18) is carried by circulating quiescent naive B cells, where its oncogenic potential would be restrained. Here, we question this current view and demonstrate that in healthy individuals, t(14;18) is actually carried by an expanding population of atypical B cells issued from germinal centers, displaying genotypic and phenotypic features of FL, and prone to constitute potent premalignant FL niches. These findings strongly impact both on the current understanding of disease progression and on the proper handling of t(14;18) frequency in blood as a potential early biomarker for lymphoma.

Abbreviations used in this paper: CSR, class-switch recombination; FL, follicular lymphoma; GC, germinal center; HI, healthy individuals; IGH, immunoglobulin heavy chain; LR-PCR, long-range PCR; SHM, somatic hypermutation.


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