Abstract
SummaryHumoral immunity consists of pre-existing antibodies expressed by long-lived plasma cells and rapidly reactive memory B cells (MBC). Recent studies of MBC development and function after protein immunization have uncovered significant MBC heterogeneity. To clarify functional roles for distinct MBC subsets during malaria infection, we generated tetramers that identify Plasmodium-specific MBCs in both humans and mice. Long-lived murine Plasmodium-specific MBCs consisted of three populations: somatically hypermutated immunoglobulin M+ (IgM+) and IgG+ MBC subsets and an unmutated IgD+ MBC population. Rechallenge experiments revealed that high affinity, somatically hypermutated Plasmodium-specific IgM+ MBCs proliferated and gave rise to antibody-secreting cells that dominated the early secondary response to parasite rechallenge. IgM+ MBCs also gave rise to T cell-dependent IgM+ and IgG+B220+CD138+ plasmablasts or T cell-independent B220−CD138+ IgM+ plasma cells. Thus, even in competition with IgG+ MBCs, IgM+ MBCs are rapid, plastic, early responders to a secondary Plasmodium rechallenge and should be targeted by vaccine strategies.
Highlights
Memory B cells (MBCs) induced by vaccine or infection are critical components of a protective humoral response
It is critical for vaccine development to understand how distinct MBC populations respond to infection
After excluding non-lymphocytes and doublets, DecoyÀMSP1+ B cells were identified among B220+ and B220lowCD138+ cells (Figures 1A and 1B)
Summary
Memory B cells (MBCs) induced by vaccine or infection are critical components of a protective humoral response. Defined MBCs express class-switched, somatically hypermutated B cell receptors (BCRs) after undergoing a GC reaction. These cells produce high-affinity antibodies within days of a secondary challenge, making them the gold standard for vaccine development. This homogeneous view of MBCs has been challenged and it is recognized that diverse MBC subsets exist in both mice and humans (Dogan et al, 2009; Klein et al, 1997; Obukhanych and Nussenzweig, 2006; Pape et al, 2011; Seifert et al, 2015). It is critical for vaccine development to understand how distinct MBC populations respond to infection
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