Plasma cell survival in the absence of B cell memory

• Published in: Nature communications 2017-11, Vol.8 (1), p.1781-11, Article 1781
• Main Authors: Hammarlund, Erika, Thomas, Archana, Amanna, Ian J., Holden, Lindsay A., Slayden, Ov D., Park, Byung, Gao, Lina, Slifka, Mark K.
• Format: Article
• Language: English
• Subjects: 631/1647/334; 631/250/1619/40/1742; 631/250/255/2514; 631/250/590/2294; Activation; Animals; Antibodies; Antibodies, Bacterial - immunology; Antibody Formation; Antigens; B-Lymphocytes - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; Bone marrow; Cell division; Cell morphology; Cell Survival; Cytology; Humanities and Social Sciences; Immunologic Memory; Immunological memory; Lymphocytes B; Macaca mulatta; Male; Memory cells; multidisciplinary; Plasma; Plasma cells; Plasma Cells - cytology; Plasma Cells - immunology; Science; Science (multidisciplinary); Survival; Vaccination; Vaccines; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-01901-w

Pre-existing serum antibodies play an important role in vaccine-mediated protection against infection but the underlying mechanisms of immune memory are unclear. Clinical studies indicate that antigen-specific antibody responses can be maintained for many years, leading to theories that reactivation/differentiation of memory B cells into plasma cells is required to sustain long-term antibody production. Here, we present a decade-long study in which we demonstrate site-specific survival of bone marrow-derived plasma cells and durable antibody responses to multiple virus and vaccine antigens in rhesus macaques for years after sustained memory B cell depletion. Moreover, BrdU + cells with plasma cell morphology can be detected for 10 years after vaccination/BrdU administration, indicating that plasma cells may persist for a prolonged period of time in the absence of cell division. On the basis of these results, long-lived plasma cells represent a key cell population responsible for long-term antibody production and serological memory. The long-term maintenance of antibody-secreting plasma cells and the requirement for memory B cells are unclear. Here, the authors show that plasma cells and the antibodies secreted are long-lived and maintained over a decade in the absence of memory B cells in non-human primates.