Plasma cell survival in the absence of B cell memory

Erika Hammarlund,Lindsay A Holden,Archana Thomas,Byung Park,Ian J Amanna,Mark K Slifka,Lina Gao,Ov D Slayden

doi:10.1038/s41467-017-01901-w

Abstract

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.

Highlights

Pre-existing serum antibodies play an important role in vaccine-mediated protection against infection but the underlying mechanisms of immune memory are unclear
Rhesus cytomegalovirus (RhCMV) causes a persistent infection in macaques and as expected, we found that the antibody responses to this virus remained stable or showed a slow increase in titers over time
Studies in rodents have shown that antibody-secreting plasma cells may survive for several weeks or months but this work is limited by the short lifespan of the host

Summary

Introduction

Pre-existing serum antibodies play an important role in vaccine-mediated protection against infection but the underlying mechanisms of immune memory are unclear. There has been a resurgence of theories regarding the potential importance of cell proliferation[13,14], persisting antigen[15,16] or non-specific activation of memory B cells[16,17,18] to sustain plasma cell numbers and antibody levels over the course of a human lifespan To investigate this question in more detail, here we show naturally acquired and vaccine-mediated immune responses in rhesus macaques that persist up to a decade after immunization and demonstrate the existence of long-lived plasma cells that can independently maintain serum antibody levels for many years in the absence of memory B cells

Methods

Results

Conclusion