Humoral immunity due to long-lived plasma cells
TL;DR: A substantial fraction of plasma cells can survive and continue to secrete antibody for extended periods of time in the absence of any detectable memory B cells, demonstrating a new mechanism by which humoral immunity is maintained.
About: This article is published in Immunity.The article was published on 1998-03-01 and is currently open access. It has received 1186 citations till now. The article focuses on the topics: Plasma cell & B-1 cell.
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TL;DR: This review addresses the heterogeneity of TCM and TEM, their differentiation stages, and the current models for their generation and maintenance in humans and mice.
Abstract: The memory T cell pool functions as a dynamic repository of antigen-experienced T lymphocytes that accumulate over the lifetime of the individual. Recent studies indicate that memory T lymphocytes contain distinct populations of central memory (TCM) and effector memory (TEM) cells characterized by distinct homing capacity and effector function. This review addresses the heterogeneity of TCM and TEM, their differentiation stages, and the current models for their generation and maintenance in humans and mice.
2,881 citations
TL;DR: It is shown that mTOR (mammalian target of rapamycin, also known as FRAP1) is a major regulator of memory CD8 T-cell differentiation, and in contrast to what was expected, the immunosuppressive drug Rapamycin has immunostimulatory effects on the generation of memoryCD8 T cells.
Abstract: Memory CD8 T cells are a critical component of protective immunity, and inducing effective memory T-cell responses is a major goal of vaccines against chronic infections and tumours. Considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory T cells. Here we show that mTOR (mammalian target of rapamycin, also known as FRAP1) is a major regulator of memory CD8 T-cell differentiation, and in contrast to what we expected, the immunosuppressive drug rapamycin has immunostimulatory effects on the generation of memory CD8 T cells. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced not only the quantity but also the quality of virus-specific CD8 T cells. Similar effects were seen after immunization of mice with a vaccine based on non-replicating virus-like particles. In addition, rapamycin treatment also enhanced memory T-cell responses in non-human primates following vaccination with modified vaccinia virus Ankara. Rapamycin was effective during both the expansion and contraction phases of the T-cell response; during the expansion phase it increased the number of memory precursors, and during the contraction phase (effector to memory transition) it accelerated the memory T-cell differentiation program. Experiments using RNA interference to inhibit expression of mTOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T cells showed that mTOR acts intrinsically through the mTORC1 (mTOR complex 1) pathway to regulate memory T-cell differentiation. Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T cells.
1,384 citations
TL;DR: It is shown 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, which offers a means to maintain serological memory for a human lifetime.
Abstract: 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.
1,312 citations
TL;DR: Quantitative analysis of serologic memory for multiple antigens in subjects followed longitudinally over the course of more than one decade suggests that peripheral memory B cells and antibody-secreting plasma cells may represent independently regulated cell populations and may play different roles in the maintenance of protective immunity.
Abstract: We performed a longitudinal analysis of antibody titers specific for viral antigens (vaccinia, measles, mumps, rubella, varicella–zoster virus, and Epstein–Barr virus) and nonreplicating antigens (tetanus and diphtheria) in 45 subjects for a period of up to 26 years. In addition, we measured antigen-specific memory B cells by means of limiting-dilution analysis, and we compared memory B-cell frequencies to their corresponding serum antibody levels. Results Antiviral antibody responses were remarkably stable, with half-lives ranging from an estimated 50 years for varicella–zoster virus to more than 200 years for other viruses such as measles and mumps. Antibody responses against tetanus and diphtheria antigens waned more quickly, with estimated half-lives of 11 years and 19 years, respectively. B-cell memory was long-lived, but there was no significant correlation between peripheral memory B-cell numbers and antibody levels for five of the eight antigens tested. Conclusions These studies provide quantitative analysis of serologic memory for multiple antigens in subjects followed longitudinally over the course of more than one decade. In cases in which multiple exposures or repeated vaccinations were common, memory B-cell numbers did not correlate with antibody titers. This finding suggests that peripheral memory B cells and antibody-secreting plasma cells may represent independently regulated cell populations and may play different roles in the maintenance of protective immunity.
1,043 citations
TL;DR: The data show that IFN-I potently enhance the primary antibody response to a soluble protein, stimulating the production of all subclasses of IgG, and induce long-lived antibody production and immunological memory.
1,010 citations
References
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TL;DR: The current understanding of the cellular basis of immune memory is reviewed and the relative contributions made to protective immunity by memory and effector T and B cells are examined.
Abstract: The immune system can remember, sometimes for a lifetime, the identity of a pathogen. Understanding how this is accomplished has fascinated immunologists and microbiologists for many years, but there is still considerable debate regarding the mechanisms by which long-term immunity is maintained. Some of the controversy stems from a failure to distinguish between effector and memory cells and to define their roles in conferring protection against disease. Here the current understanding of the cellular basis of immune memory is reviewed and the relative contributions made to protective immunity by memory and effector T and B cells are examined.
1,774 citations
"Humoral immunity due to long-lived ..." refers background in this paper
...In our experiments monitoring plasma cell survival, we found that the rate of plasma induce prolonged serum antibody responses (Plotkin and Mortimer, 1988; Ahmed and Gray, 1996; Slifka and cell decline was similar irrespective of age and that the half-life of plasma cells in young mice, at 2–4 months Ahmed, 1996b)....
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Book•
01 Jan 1976
TL;DR: This text and review has been updated and revised since the last edition in 1974 and features include emphasis on normal immunologic function and disease processes.
Abstract: This text and review has been updated and revised since the last edition in 1974. The normal immunologic function and disease processes are presented clearly. New features include emphasis on normal immunologic function and disease processes; a new immunotherapy section describing drugs and other therapies; an updated immunologic laboratory tests section featuring new methods and techniques; a chapter on molecular genetic techniques for clinical analysis of the immune system; and numerous illustrations. This work is intended for students, physicians and biotechnology professionals.
1,524 citations
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TL;DR: The Th1/Th2 paradigm provides a useful model for understanding the pathogenesis of several diseases, as well as for developing novel immunotherapeutic strategies, and is examined in the context of associated pathophysiological conditions.
1,145 citations
TL;DR: It is shown that antibody-secreting plasma cells from bone marrow are as long-lived as memory B cells.
Abstract: Immune protection is based on long-lived memory cells and effector cells, which are either cytotoxic or secrete antibodies. The lifespan of these effector cells has not so far been determined. Here we show that antibody-secreting plasma cells from bone marrow are as long-lived as memory B cells.
841 citations
"Humoral immunity due to long-lived ..." refers result in this paper
...Consistent with our findings, a immunization with live viral vaccines such as those recent study (Manz et al., 1997) that examined plasma against measles, polio, and yellow fever, or even inert vaccines such as those against tetanus or diphtheria cell longevity in the bone marrow showed that plasma toxoid, result in circulating antibody in the serum that cells can survive for more than 90 days without turnover....
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...To maintain a stable population of plasma cells, the rate of generation of plasma cells by differentiation In agreement with our data describing long-lived plasma cells, a recent study (Manz et al., 1997) has used of memory B cells must, in turn, equal the rate at which they die (p P)....
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TL;DR: The results show that LCMV variants that emerge during infection in vivo play a crucial role in the suppression of virus-specific CTL responses and in the maintenance of virus persistence.
Abstract: We studied the mechanism of lymphocytic choriomeningitis virus (LCMV) persistence and the suppression of cytotoxic T lymphocyte (CTL) responses in BALB/c WEHI mice infected at birth with LCMV Armstrong strain. Using adoptive transfer experiments we found that spleen cells from persistently infected (carrier) mice actively suppressed the expected LCMV-specific CTL response of spleen cells from normal adult mice. The suppression was specific for the CTL response and LCMV -specific antibody responses were not affected. Associated with the specific CTL suppression was the establishment of persistent LCMV infection. The transfer of spleen or lymph node cells containing LCMV -specific CTL resulted in virus clearance and prevented establishment of the carrier state. The suppression of LCMV -specific CTL responses by carrier spleen cells is not mediated by a suppressor cell, but is due to the presence of genetic variants of LCMV in spleens of carrier mice. Such virus variants selectively suppress LCMV-specific CTL responses and cause persistent infections in immunocompetent mice. In striking contrast, wild-type LCMV Armstrong, from which these variants were generated, induces a potent CTL response in immunocompetent mice and the LCMV infection is rapidly cleared. Our results show that LCMV variants that emerge during infection in vivo play a crucial role in the suppression of virus-specific CTL responses and in the maintenance of virus persistence.
762 citations
"Humoral immunity due to long-lived ..." refers background in this paper
...Nonadherviously (Ahmed et al., 1984)....
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...The levels of LCMV-specific IgG (A), IgG1 (B), and IgG2a (C) in the serum of these mice were determined the rate of antibody production per plasma cell does not by ELISA (Ahmed et al., 1984)....
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...ELISA (Ahmed et al., 1984) and measured in ELISA units....
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