Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice
| Autor: | Dorothy H. L. Ng, Jean Langhorne, Eunice Nduati, Emma Tamsin Cadman, Joshua F Coulcher, Douglas William MacDonald, Francis M. Ndungu, Elisabeth Couper |
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| Rok vydání: | 2009 |
| Předmět: |
Antibodies
Protozoan Cell Separation Plasmodium chabaudi Mice 0302 clinical medicine Biology (General) Memory B cell Merozoite Surface Protein 1 B-Lymphocytes 0303 health sciences biology Flow Cytometry Acquired immune system 3. Good health medicine.anatomical_structure Female Antibody Research Article Infectious Diseases/Tropical and Travel-Associated Diseases QH301-705.5 Plasma Cells Immunology Naive B cell Enzyme-Linked Immunosorbent Assay Microbiology 03 medical and health sciences Immunology/Immunity to Infections Virology Genetics medicine Animals Molecular Biology B cell 030304 developmental biology Infectious Diseases/Protozoal Infections RC581-607 biology.organism_classification Malaria Mice Inbred C57BL B-1 cell Antibody Formation biology.protein Parasitology Bone marrow Immunologic diseases. Allergy Immunologic Memory 030215 immunology |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 5, Iss 12, p e1000690 (2009) |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1000690 |
| Popis: | 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. Author Summary Malaria causes considerable human suffering resulting from associated high mortality, morbidity and reduced economic productivity in endemic areas. Current control methods are thwarted by a multiplicity of problems including rapidly developing resistance for anti-malarial drugs and insecticide-treated nets, and huge costs and hence poor coverage with bed nets in poor countries. Understanding the basis of the inefficiency of immunity to malaria in childhood will greatly aid the search for effective vaccines, which together with drugs and vector control, will be essential in the drive to eliminate malaria. Because of the strong evidence associating anti-malarial antibodies with anti-parasitic and anti-disease effects, vaccines inducing protective long-lasting antibody responses are attractive. However, it has been suggested that antibody responses to some Plasmodium antigens may be not long-lived. It would be important to determine whether long-lived plasma cells and memory B cells are generated after a malaria infection; however, these studies are difficult to perform in humans. Therefore we investigated the kinetics, duration and characteristics of the two cell types responsible for long-term antibody production in a mouse model of malaria. We show here that malaria-specific memory B cells and plasma cells are still detectable more than eight months after infection, and that both long-lived malaria-specific antibody-secreting cells and functional malaria-specific memory B cells can be made after a single infection. |
| Databáze: | OpenAIRE |
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