The TLR9 ligand CpG promotes the acquisition of Plasmodium falciparum-specific memory B cells in malaria-naive individuals

Peter D. Crompton, Marko Mircetic, Greta Weiss, Amy Baughman, Chiung Yu Huang, David J. Topham, John J. Treanor, Iñaki Sanz, F. Eun Hyung Lee, Anna P. Durbin, Kazutoyo Miura, David L. Narum, Ruth D. Ellis, Elissa Malkin, Gregory E.D. Mullen, Louis H. Miller, Laura B. Martin, Susan K. Pierce

Research output: Contribution to journalArticlepeer-review

Abstract

Despite the central role of memory B cells (MBC) in protective immune responses, little is understood about how they are acquired in naive individuals in response to Ag exposure, and how this process is influenced by concurrent activation of the innate immune system's TLR. In this longitudinal study of malaria-naive individuals, we examined the MBC response to two candidate malaria vaccines administered with or without CpG, a TLR9 ligand. We show that the acquisition of MBC is a dynamic process in which the vaccine-specific MBC pool rapidly expands and then contracts, and that CpG enhances the kinetics, magnitude, and longevity of this response. We observed that the percentage of vaccine-specific MBC present at the time of reimmunization predicts vaccine-specific Ab levels 14 days later; and that at steady-state, there is a positive correlation between vaccine-specific MBC and Ab levels. An examination of the total circulating MBC and plasma cell pools also suggests that MBC differentiate into plasma cells through polyclonal activation, independent of Ag specificity. These results provide important insights into the human MBC response, which can inform the development of vaccines against malaria and other pathogens that disrupt immunological memory.

Original languageEnglish (US)
Pages (from-to)3318-3326
Number of pages9
JournalJournal of Immunology
Volume182
Issue number5
DOIs
StatePublished - Mar 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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