Recovery of an antiviral antibody response following attrition caused by unrelated infection

• Published in: PLoS pathogens Vol. 10; no. 1; p. e1003843
• Main Authors: Ng, Dorothy H L, Skehel, John J, Kassiotis, George, Langhorne, Jean
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2014; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies, Viral - immunology; Antigens; Antiviral agents; Bone marrow; Dosage and administration; Drug interactions; Homeostasis; Immune system; Immunity, Humoral; Influenza A virus - immunology; Malaria - immunology; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - pathology; Parasites; Pharmaceutical research; Plasma Cells - immunology; Plasma Cells - pathology; Plasmodium chabaudi - immunology; Receptors, IgG - immunology; Rodents; Time Factors; United Kingdom
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003843

The homeostatic mechanisms that regulate the maintenance of immunological memory to the multiple pathogen encounters over time are unknown. We found that a single malaria episode caused significant dysregulation of pre-established Influenza A virus-specific long-lived plasma cells (LLPCs) resulting in the loss of Influenza A virus-specific Abs and increased susceptibility to Influenza A virus re-infection. This loss of LLPCs involved an FcγRIIB-dependent mechanism, leading to their apoptosis. However, given enough time following malaria, the LLPC pool and humoral immunity to Influenza A virus were eventually restored. Supporting a role for continuous conversion of Influenza A virus-specific B into LLPCs in the restoration of Influenza A virus immunity, B cell depletion experiments also demonstrated a similar requirement for the long-term maintenance of serum Influenza A virus-specific Abs in an intact LLPC compartment. These findings show that, in addition to their established role in the anamnestic response to reinfection, the B cell pool continues to be a major contributor to the maintenance of long-term humoral immunity following primary Influenza A virus infection, and to the recovery from attrition following heterologous infection. These data have implications for understanding the longevity of protective efficacy of vaccinations in countries where continuous infections are endemic.