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Science 13 December 2002:
Vol. 298. no. 5601, pp. 2199 - 2202
DOI: 10.1126/science.1076071
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Reports

Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells

Nadia L. Bernasconi,* Elisabetta Traggiai,* Antonio Lanzavecchiadagger

Production of antibodies can last for a lifetime, through mechanisms that remain poorly understood. Here, we show that human memory B lymphocytes proliferate and differentiate into plasma cells in response to polyclonal stimuli, such as bystander T cell help and CpG DNA. Furthermore, plasma cells secreting antibodies to recall antigens are produced in vivo at levels proportional to the frequency of specific memory B cells, even several years after antigenic stimulation. Although antigen boosting leads to a transient increase in specific antibody levels, ongoing polyclonal activation of memory B cells offers a means to maintain serological memory for a human lifetime.

Institute for Research in Biomedicine, Via Vela 6, CH 6500 Bellinzona, Switzerland.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: lanzavecchia{at}irb.unisi.ch

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Persistent Humoral Immune Defect in Highly Active Antiretroviral Therapy-Treated Children With HIV-1 Infection: Loss of Specific Antibodies Against Attenuated Vaccine Strains and Natural Viral Infection.
V. Bekker, H. Scherpbier, D. Pajkrt, S. Jurriaans, H. Zaaijer, and T. W. Kuijpers (2006)
Pediatrics 118, e315-e322
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Clinical Relevance of Different IgG and IgM Serum Antibody Responses to Borrelia burgdorferi After Antibiotic Therapy for Erythema Migrans: Long-term Follow-up Study of 113 Patients..
M. Glatz, M. Golestani, H. Kerl, and R. R. Mullegger (2006)
Arch Dermatol 142, 862-868
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Antibody Production and In Vitro Behavior of CD27-Defined B-Cell Subsets: Persistent Hepatitis C Virus Infection Changes the Rules..
V. Racanelli, M. A. Frassanito, P. Leone, M. Galiano, V. De Re, F. Silvestris, and F. Dammacco (2006)
J. Virol. 80, 3923-3934
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Immunization-Induced Perturbation of Human Blood Plasma Cell Pool: Progressive Maturation, IL-6 Responsiveness, and High PRDI-BF1/BLIMP1 Expression Are Critical Distinctions between Antigen-Specific and Nonspecific Plasma Cells.
I. Gonzalez-Garcia, E. Ocana, G. Jimenez-Gomez, A. Campos-Caro, and J. A. Brieva (2006)
J. Immunol. 176, 4042-4050
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Rheumatoid factors: what's new?.
O. M. R. Westwood, P. N. Nelson, and F. C. Hay (2006)
Rheumatology 45, 379-385
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Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific.
G. D. Genova, J. Roddick, F. McNicholl, and F. K. Stevenson (2006)
Blood 107, 2806-2813
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A checkpoint for autoreactivity in human IgM+ memory B cell development.
M. Tsuiji, S. Yurasov, K. Velinzon, S. Thomas, M. C. Nussenzweig, and H. Wardemann (2006)
J. Exp. Med. 203, 393-400
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Role of MHC Class II on Memory B Cells in Post-Germinal Center B Cell Homeostasis and Memory Response.
M. Shimoda, T. Li, J. P. S. Pihkala, and P. A. Koni (2006)
J. Immunol. 176, 2122-2133
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Expression and Regulation of the Orphan Receptor RDC1 and Its Putative Ligand in Human Dendritic and B Cells.
S. Infantino, B. Moepps, and M. Thelen (2006)
J. Immunol. 176, 2197-2207
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Human Interleukin-15 Improves Engraftment of Human T Cells in NOD-SCID Mice.
A. Sun, H. Wei, R. Sun, W. Xiao, Y. Yang, and Z. Tian (2006)
Clin. Vaccine Immunol. 13, 227-234
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Immunological Memory: The Role of B Cells in Long-term Protection Against Invasive Bacterial Pathogens.
D. F. Kelly, A. J. Pollard, and E. R. Moxon (2005)
JAMA 294, 3019-3023
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Activation of naive B lymphocytes via CD81, a pathogenetic mechanism for hepatitis C virus-associated B lymphocyte disorders.
D. Rosa, G. Saletti, E. De Gregorio, F. Zorat, C. Comar, U. D'Oro, S. Nuti, M. Houghton, V. Barnaba, G. Pozzato, et al. (2005)
PNAS 102, 18544-18549
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Antibody Repertoire Development in Fetal and Neonatal Piglets. IX. Three Pathogen-Associated Molecular Patterns Act Synergistically to Allow Germfree Piglets to Respond to Type 2 Thymus-Independent and Thymus-Dependent Antigens.
J. E. Butler, D. H. Francis, J. Freeling, P. Weber, and A. M. Krieg (2005)
J. Immunol. 175, 6772-6785
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How does B cell depletion therapy work, and how can it be improved?.
E A Clark and J A Ledbetter (2005)
Ann Rheum Dis 64, iv77-iv80
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Vaccinia Virus H3L Envelope Protein Is a Major Target of Neutralizing Antibodies in Humans and Elicits Protection against Lethal Challenge in Mice.
D. H. Davies, M. M. McCausland, C. Valdez, D. Huynh, J. E. Hernandez, Y. Mu, S. Hirst, L. Villarreal, P. L. Felgner, and S. Crotty (2005)
J. Virol. 79, 11724-11733
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Regulation of Aged Humoral Immune Defense against Pneumococcal Bacteria by IgM Memory B Cell.
Y. Shi, T. Yamazaki, Y. Okubo, Y. Uehara, K. Sugane, and K. Agematsu (2005)
J. Immunol. 175, 3262-3267
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