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, Raymond Borrow, Robert S. Heyderman, Adam Finn

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    15 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 B MEM. 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 B MEM 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)6071-6086
    Number of pages16
    JournalJournal of Immunology
    Volume191
    Issue number12
    DOIs
    Publication statusPublished - 15 Dec 2013

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