Polysaccharide-specific memory B cells generated by conjugate vaccines in humans conform to the CD27+IgG+ isotype-switched memory B Cell phenotype and require contact-dependent signals from bystander T cells activated by bacterial proteins to differentiate into plasma cells

Edward T Clarke, Neil A Williams, Jamie Findlow, Ray Borrow, Robert S Heyderman, Adam Finn

Research output: Contribution to journalArticle (Academic Journal)

12 Citations (Scopus)

Abstract

The polysaccharides (PS) surrounding encapsulated bacteria are generally unable to activate T cells and hence do not induce B cell memory (BMEM). PS conjugate vaccines recruit CD4(+) T cells via a carrier protein, such as tetanus toxoid (TT), resulting in the induction of PS-specific BMEM. However, the requirement for T cells in the subsequent activation of the BMEM at the time of bacterial encounter is poorly understood, despite having critical implications for protection. We demonstrate that the PS-specific BMEM induced in humans by a meningococcal serogroup C PS (Men C)-TT conjugate vaccine conform to the isotype-switched (IgG(+)CD27(+)) rather than the IgM memory (IgM(+)CD27(+)) phenotype. Both Men C and TT-specific BMEM require CD4(+) T cells to differentiate into plasma cells. However, noncognate bystander T cells provide such signals to PS-specific BMEM with comparable effect to the cognate T cells available to TT-specific BMEM. The interaction between the two populations is contact-dependent and is mediated in part through CD40. Meningococci drive the differentiation of the Men C-specific BMEM through the activation of bystander T cells by bacterial proteins, although these signals are enhanced by T cell-independent innate signals. An effect of the TT-specific T cells activated by the vaccine on unrelated BMEM in vivo is also demonstrated. These data highlight that any protection conferred by PS-specific BMEM at the time of bacterial encounter will depend on the effectiveness with which bacterial proteins are able to activate bystander T cells. Priming for T cell memory against bacterial proteins through their inclusion in vaccine preparations must continue to be pursued.

Original languageEnglish
Pages (from-to)6071-83
Number of pages13
JournalJournal of Immunology
Volume191
Issue number12
DOIs
Publication statusPublished - 15 Dec 2013

Keywords

  • Antigen Presentation
  • Antigens, Bacterial
  • Antigens, CD27
  • B-Lymphocyte Subsets
  • Bystander Effect
  • Humans
  • Immunoglobulin Class Switching
  • Immunoglobulin G
  • Immunologic Memory
  • Immunophenotyping
  • Leukocytes, Mononuclear
  • Lymphocyte Activation
  • Lymphocyte Cooperation
  • Lymphopoiesis
  • Models, Immunological
  • Neisseria meningitidis, Serogroup C
  • Palatine Tonsil
  • Plasma Cells
  • Polysaccharides, Bacterial
  • Receptors, Antigen, B-Cell
  • T-Lymphocyte Subsets
  • Tetanus Toxoid
  • Vaccines, Conjugate

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