IgM Memory Cells: First Responders in Malaria Sara L. Stone, Frances E. Lund  Immunity  Volume 45, Issue 2, Pages 235-237 (August 2016) DOI: 10.1016/j.immuni.2016.08.005 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Mutated P. chabaudi-Specific IgM+ Memory B Cells Seed Early Secondary T-Cell-Dependent Plasmablast and T-Cell-Independent Plasma Cell Responses (Top left) Approximately 100 days after primary infection with P. chabaudi-infected red blood cells (iRBCs, model at the bottom left), three populations of memory and naive cells (B220+CD38+CD138−GL7−) specific to P. chabaudi MSP1 were identified by flow cytometry using labeled recombinant MSP1 tetramers. 50% of the MSP1+ memory B cells retained expression of IgD+ (IgD+ MBCs), 20% expressed IgM and not IgD (IgM+ MBCs), and 30% had undergone class-switch recombination and expressed neither IgD nor IgM (IgM− MBCs). Cloning and expression of the BCRs from all three MBC populations revealed that each of the MBC subsets was specific to MSP1; however, the BCRs were somatically mutated only in the IgM+ and IgM− MBC populations. Likewise, only the MSP1+IgM+ and MSP1+IgM− MBC populations, isolated 2 days after challenge infection with iRBCs, were competent to differentiate into antibody-secreting cells in vitro. (Top right) Splenic MSP1+ PBs and PCs were identified within 3 days of challenge infection. The majority (∼80%) of MSP1+ PBs and PCs produced somatically mutated IgM antibodies. Furthermore, serum IgM, but not IgG, MSP1-specific antibody titers were increased at this time point. CD4 depletion at the time of challenge infection revealed that the MSP1+ PB response, but not the MSP1+ PC response, required T cell help. Thus, the rapid secondary antibody response to re-infection with P. chabaudi is controlled by both T-cell-dependent and T-cell-independent signals and is mediated largely by the IgM+ MBC population. (Bottom right) P. chabaudi infection in mice induced not only MSP1-binding MBCs, PBs, and PCs but also GC B cells and GC precursors. MSP1-binding B cells were also detected in peripheral-blood mononuclear cells (PBMCs) from malaria-infected individuals, but not in unexposed control individuals. Immunity 2016 45, 235-237DOI: (10.1016/j.immuni.2016.08.005) Copyright © 2016 Elsevier Inc. Terms and Conditions