Mechanisms of Humoral Immunity Explored Through Studies of LCMV Infection
Prolonged synthesis of antigen-specific antibody is one of the cardinal features of successful vaccination and one of the key parameters used to demonstrate immunological memory. For years, long-term antibody production was attributed solely to the contin
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SLIFKA
Introduction 2 4
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LCMV Model System
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Long-Term Humoral Immunity Following Viral Infection
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Anatomical Sites of Antiviral Antibody Production
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5 Mechanisms of Long-Term Humoral Immunity 5.1 Antigen-Dependent Models for Maintaining Antibody Production. 5.2 Antigen-Independent Model for Maintaining Antibody Production: Long-Lived Plasma Cells 6
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Conclusions.
References
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1 Introduction Prolonged synthesis of antigen-specific antibody is one of the cardinal features of successful vaccination and one of the key parameters used to demonstrate immunological memory. For years, long-term antibody production was attributed solely to the continuous stimulation and differentiation of memory B cells into antibodysecreting plasma cells. However, several studies have now revealed that long-lived plasma cells, most of which reside in the bone marrow, represent a previously overlooked mechanism for sustaining long-term humoral immunity. In this regard, analysis of the antiviral antibody response that occurs following acute infection with lymphocytic choriomeningitis virus (LCMV) has been instrumental in developing our current understanding of the mechanisms underlying long-term antibody synthesis.
OHSU Vaccine and Gene Therapy Institute, 505 NW 185th Avenue. Beaverton. OR 97006, USA
M. B. A. Oldstone (ed.), Arenaviruses II © Springer-Verlag Berlin Heidelberg 2002
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M.K. Slifka
2 LCMV Model System LCMV is a common munne pathogen that provides an excellent model for studying the interactions between a virus and the immune system of its natural host (OLDSTONE and DIXON 1967; BUCHMEIER et al. 1980; LEHMANN-GRUBE et al. 1983; OLDSTONE et al. 1985; AHMED and GRAY 1996). Infection of adult mice with LCMV-Armstrong results in an acute infection that is cleared within 1 to 2 weeks in a perforin-mediated (WALSH et al. 1994; KAGI et al. 1994), CD8 I T cell-dependent manner (ZINKERNAGEL and DOHERTY 1979; BUCHMEIER et al. 1980; BYRNE and OLDSTONE 1984; AHMED et al. 1984; LEHMANN-GRUBE et al. 1985; WHITTON et al. 1993; WELSH and McNALLY 1999). B cells and/or neutralizing antibodies are not required for viral clearance (CERNY et al. 1988; ASANO and AHMED 1996; BRUNDLER et al. 1996) but may playa substantial role in decreasing viral load (CERNY et al. 1988; WRIGHT and BUCHMEIER 1991; BATTEGAY et al. 1993; SEILER et al. 1998a,b) and act synergistically with antiviral T cells to prevent reinfection (THOMSEN and MARKER 1988; BALDRIDGE et al. 1997). Recovery from acute LCMV infection invariably leads to long-term T cell and B cell memory (BUCHMEIER et al. 1980; LAU et al. 1994; SLIFKA et al. 1998; OCHSENBEIN et al. 2000) and persistence of antiviral serum antibody for the life span of immunocompetent mice (KIMMIG and LEHMANN-GRUBE 1979; SLIFKA et al. 1995, 1998; OCHSENBEIN et al. 2000).
3 Long-Term Humoral Immunity Following Viral Infection How long can antigen-specific antibody responses be maintained in humans'? Following systemic viral infection, it is not uncommon for antiviral antibody responses
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