Functional memory B cells and long-lived plasma cells are generated after a single Plasmodium chabaudi infection in mice

• Published in: PLoS pathogens 2009-12, Vol.5 (12), p.e1000690-1000690
• Main Authors: Ndungu, Francis Maina, Cadman, Emma Tamsin, Coulcher, Joshua, Nduati, Eunice, Couper, Elisabeth, Macdonald, Douglas William, Ng, Dorothy, Langhorne, Jean
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Protozoan - immunology; Antibody Formation - immunology; B cells; B-Lymphocytes - immunology; Cell Separation; Development and progression; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Immune system; Immunoglobulins; Immunologic Memory - immunology; Immunology/Immunity to Infections; Infectious Diseases/Protozoal Infections; Infectious Diseases/Tropical and Travel-Associated Diseases; Malaria; Malaria - immunology; Medicin och hälsovetenskap; Merozoite Surface Protein 1 - immunology; Mice; Mice, Inbred C57BL; Physiological aspects; Plasma; Plasma cells; Plasma Cells - immunology; Plasmodium; Plasmodium chabaudi; Plasmodium chabaudi - immunology; Proteins
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000690

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.