Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

Matthias F Muellenbeck, Beatrix Ueberheide, Borko Amulic, Alexandra Epp, David Fenyo, Christian E Busse, Meral Esen, Michael Theisen, Benjamin Mordmüller, Hedda Wardemann

Research output: Contribution to journalArticle (Academic Journal)peer-review

120 Citations (Scopus)

Abstract

Antibodies can protect from Plasmodium falciparum (Pf) infection and clinical malaria disease. However, in the absence of constant reexposure, serum immunoglobulin (Ig) levels rapidly decline and full protection from clinical symptoms is lost, suggesting that B cell memory is functionally impaired. We show at the single cell level that natural Pf infection induces the development of classical memory B cells (CM) and atypical memory B cells (AtM) that produce broadly neutralizing antibodies against blood stage Pf parasites. CM and AtM contribute to anti-Pf serum IgG production, but only AtM show signs of active antibody secretion. AtM and CM were also different in their IgG gene repertoire, suggesting that they develop from different precursors. The findings provide direct evidence that natural Pf infection leads to the development of protective memory B cell antibody responses and suggest that constant immune activation rather than impaired memory function leads to the accumulation of AtM in malaria. Understanding the memory B cell response to natural Pf infection may be key to the development of a malaria vaccine that induces long-lived protection.

Original languageEnglish
Pages (from-to)389-99
Number of pages11
JournalJournal of Experimental Medicine
Volume210
Issue number2
DOIs
Publication statusPublished - 11 Feb 2013

Keywords

  • Adult
  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • B-Lymphocyte Subsets
  • Erythrocytes
  • Host-Parasite Interactions
  • Humans
  • Immunoglobulin G
  • Immunoglobulin Variable Region
  • Immunologic Memory
  • Malaria Vaccines
  • Malaria, Falciparum
  • Middle Aged
  • Molecular Sequence Data
  • Plasmodium falciparum
  • Protozoan Proteins
  • Young Adult
  • Journal Article
  • Research Support, Non-U.S. Gov't

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