Abstract
Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. Antigen-activated B cells—with T-cell help—undergo affinity maturation within germinal centres and persist as long-lived IgG plasma cells in the bone marrow. Here we show that antigen-specific, induced IgM plasma cells also persist for a lifetime. Unlike long-lived IgG plasma cells, which develop in germinal centres and then home to the bone marrow, IgM plasma cells are primarily retained within the spleen and can develop even in the absence of germinal centres. Interestingly, their expressed IgV loci exhibit somatic mutations introduced by the activation-induced cytidine deaminase (AID). However, these IgM plasma cells are probably not antigen-selected, as replacement mutations are spread through the variable segment and not enriched within the CDRs. Finally, antibodies from long-lived IgM plasma cells provide protective host immunity against a lethal virus challenge.
Highlights
Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies
This process typically selects for replacement mutations at higher frequency within the antigen-binding, complementary determining regions (CDRs) than in framework regions, as is commonly seen in both memory B cells and IgG LLPCs4,11
We found long-lived IgM responses in the spleen, significantly above naive controls, in particular in the infected cohorts. We extended these studies to infection with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) (Fig. 1g,h) and again observed significantly higher numbers of antigen-specific, IgM long-lived plasma cells (LLPCs) in the spleen compared with naive controls
Summary
Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. 6 Department of Immunobiology, Yale University School of Medicine, Yale University, New Haven, Connecticut 74085, Immune memory can last a lifetime, in no small part due to antigen-specific, long-lived plasma cells (LLPCs) that continuously secrete antibodies and provide long-term protection[1,2,3,4,5]. These plasma cells (PCs) develop from antigenspecific B cells through one of two pathways, resulting in either short-lived PCs or LLPCs. Following activation, antigen-specific B cells are able to progress immediately into short-lived PCs without T-cell help. IgM LLPCs were found to protect against viral challenge in vivo
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