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Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice

Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infection...

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Autores principales: Ndungu, Francis Maina, Cadman, Emma Tamsin, Coulcher, Joshua, Nduati, Eunice, Couper, Elisabeth, MacDonald, Douglas William, Ng, Dorothy, Langhorne, Jean
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784955/
https://www.ncbi.nlm.nih.gov/pubmed/20011127
http://dx.doi.org/10.1371/journal.ppat.1000690
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author Ndungu, Francis Maina
Cadman, Emma Tamsin
Coulcher, Joshua
Nduati, Eunice
Couper, Elisabeth
MacDonald, Douglas William
Ng, Dorothy
Langhorne, Jean
author_facet Ndungu, Francis Maina
Cadman, Emma Tamsin
Coulcher, Joshua
Nduati, Eunice
Couper, Elisabeth
MacDonald, Douglas William
Ng, Dorothy
Langhorne, Jean
author_sort Ndungu, Francis Maina
collection PubMed
description Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice. Memory B cells and plasma cells specific for the C-terminal region of Merozoite Surface Protein 1 were detectable for more than eight months following primary infection. Furthermore, a classical memory response comprised predominantly of the T-cell dependent isotypes IgG2c, IgG2b and IgG1 was elicited upon rechallenge with the homologous parasite, confirming the generation of functional memory B cells. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, we demonstrated long-lived cells secreting Plasmodium-specific IgG in both bone marrow and in spleens of infected mice. The presence of these long-lived cells was independent of the presence of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, both functional Plasmodium-specific memory B cells and long-lived plasma cells can be generated, suggesting that defects in generating these cell populations may not be the reason for generating short-lived antibody responses.
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spelling pubmed-27849552009-12-15 Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice Ndungu, Francis Maina Cadman, Emma Tamsin Coulcher, Joshua Nduati, Eunice Couper, Elisabeth MacDonald, Douglas William Ng, Dorothy Langhorne, Jean PLoS Pathog Research Article Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice. Memory B cells and plasma cells specific for the C-terminal region of Merozoite Surface Protein 1 were detectable for more than eight months following primary infection. Furthermore, a classical memory response comprised predominantly of the T-cell dependent isotypes IgG2c, IgG2b and IgG1 was elicited upon rechallenge with the homologous parasite, confirming the generation of functional memory B cells. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, we demonstrated long-lived cells secreting Plasmodium-specific IgG in both bone marrow and in spleens of infected mice. The presence of these long-lived cells was independent of the presence of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, both functional Plasmodium-specific memory B cells and long-lived plasma cells can be generated, suggesting that defects in generating these cell populations may not be the reason for generating short-lived antibody responses. Public Library of Science 2009-12-11 /pmc/articles/PMC2784955/ /pubmed/20011127 http://dx.doi.org/10.1371/journal.ppat.1000690 Text en Ndungu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ndungu, Francis Maina
Cadman, Emma Tamsin
Coulcher, Joshua
Nduati, Eunice
Couper, Elisabeth
MacDonald, Douglas William
Ng, Dorothy
Langhorne, Jean
Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice
title Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice
title_full Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice
title_fullStr Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice
title_full_unstemmed Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice
title_short Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice
title_sort functional memory b cells and long-lived plasma cells are generated after a single plasmodium chabaudi infection in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784955/
https://www.ncbi.nlm.nih.gov/pubmed/20011127
http://dx.doi.org/10.1371/journal.ppat.1000690
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