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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4653-4659.
Prepublished online as a Blood First Edition Paper on March 3, 2008; DOI 10.1182/blood-2007-11-123844.


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IMMUNOBIOLOGY

The human spleen is a major reservoir for long-lived vaccinia virus–specific memory B cells

Maria Mamani-Matsuda1, Antonio Cosma2,3, Sandra Weller1, Ahmad Faili1, Caroline Staib3,4, Loïc Garçon5, Olivier Hermine6, Odile Beyne-Rauzy7, Claire Fieschi8, Jacques-Olivier Pers9, Nina Arakelyan10, Bruno Varet6, Alain Sauvanet11, Anne Berger12, François Paye13, Jean-Marie Andrieu10, Marc Michel14, Bertrand Godeau14, Pierre Buffet15, Claude-Agnès Reynaud1, and Jean-Claude Weill1

1 Inserum U783, "Développement du Système Immunitaire," Université Paris Descartes, Faculté de Médecine, Site Necker-Enfants Malades, Paris, France; 2 Clinical cooperation group "Immune monitoring," Helmholtz Zentrum München-German Research Center for Environmental Health, Munich, Germany; 3 Institute of Molecular Virology and Clinical cooperation group "Antigen-specific immunotherapy," Helmhotz Zentrum München-German Research Center for Environmental Health, Munich, Germany; 4 Institute of Virology, Technical University, Munich, Germany; 5 Centre Hospitalier Universitaire (CHU) Bicêtre, Service d'Hématologie, Le Kremlin-Bicêtre, France; 6 Hôpital Necker-Enfants Malades, Service d'Hématologie adulte, Paris, France; 7 CHU de Toulouse, Service de Médecine Interne et Immunopathologie, Toulouse, France; 8 Hôpital Saint-Louis, Unité d'Immunopathologie, Paris, France; 9 CHU de Brest, Laboratoire d'Immunologie et Pathologie, Brest, France; 10 Hôpital Européen Georges Pompidou, Service de Cancérologie, Paris, France; 11 Hôpital Beaujon, Service de Chirurgie Digestive, Clichy, France; 12 Hôpital Européen Georges Pompidou, Service de Chirurgie Digestive, Paris, France; 13 Hôpital Saint Antoine, Service de Chirurgie Digestive, Paris, France; 14 CHU Henri Mondor, Service de Médecine Interne, Créteil, France; and 15 Centre Médical, Institut Pasteur, Paris, France

The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compartments present similar frequencies of IgG+ cells, antismallpox memory B cells are specifically enriched in the spleen where they account for 0.24% of all IgG+ cells (ie, 10-20 million cells) more than 30 years after vaccination. They represent, in contrast, only 0.07% of circulating IgG+ B cells in blood (ie, 50-100 000 cells). An analysis of patients either splenectomized or rituximab-treated confirmed that the spleen is a major reservoir for long-lived memory B cells. No significant correlation was observed between the abundance of these cells in blood and serum titers of antivaccinia virus antibodies in this study, including in the contrasted cases of B cell– depleting treatments. Altogether, these data provide evidence that in humans, the two arms of B-cell memory—long-lived memory B cells and plasma cells—have specific anatomic distributions—spleen and bone marrow—and homeostatic regulation.


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