Induction and Maintenance of Long-Term Immunological Memory Following Infection or Vaccination

Immunological memory is the underlying hallmark of vaccination. However, the mechanisms underlying the induction and maintenance of memory remain poorly understood. The most commonly accepted theory is that long-lived memory lymphocytes, as opposed to short-lived acute effector lymphocytes, maintain memory. In recent years, there has been an increasing number of studies on the induction of memory following vaccination with live vectors or infection with replicating viruses or bacteria. However, it is currently unclear (i) how a putative population of long-lived lymphocytes is induced following vaccination with non-replicating vectors or adjuvants; (ii) whether they derive from different clones than the acute effectors, and indeed, (iii) how they manage to live for decades while acute effectors are programmed to die within weeks. Although there are studies showing that memory B cells can engage neighboring naïve T cells, the mechanisms that dictate how long-lived memory CD4+ helper T cells can exist for decades, presumably separately from their cooperating long-lived B cells and CTLs, and then be subsequently engaged when the recall antigen is encountered remain elusive.

Another hypothesis on the maintenance of long-term memory is that our lymph nodes act as libraries of millions of antigens that we encounter since birth, and that these antigens, through unknown mechanisms, keep antigen-specific clones in a state of threshold activation, without causing them to undergo terminal differentiation - the fate of their acute effector sister clones. There is yet another more recent hypothesis proposing that upon encounter with recall antigens, strong pro-inflammatory signals trigger rare clones of long-lived memory cells to undergo rapid proliferation and differentiation into memory effectors.

While long-term B cell memory is thought to be maintained by long-lived IgG or IgA secreting cells, it has been proposed that it is also maintained by low avidity IgM-secreting cells which can rapidly proliferate and differentiate into high avidity IgG- or IgA-secreting cells upon encounter with recall antigen. Whether there is a fundamental difference in long-term memory induction following mucosal versus systemic vaccination or infection is also unclear, but warrants further study since there are fundamental differences in the structure and individual cell populations that populate mucosal versus systemic sites of pathogen entry. Although more recently there have been reports on short–term NK memory cells, reports on the presence of long-term memory NK cells are scarce, and thus the focus of this Research Topic will be on long-term memory B and T cells.

In this Research Topic, we welcome the submission of Review, Mini-Review and Original Research articles that shed long-needed light on how long-term B, CD4+ T helper and CD8+ CTL memory is induced and maintained following infection or vaccination. Mechanistic studies in animal models as well as in humans that distinguish acute effectors from long-term resting and effector memory clones, both phenotypically and functionally, are encouraged to be submitted. In particular, studies that follow the kinetics of long-term memory formation in terms of phenotypic and functional characterization of antigen-specific B, CD4+ and CD8+ T cells following initial encounter with a specific antigen, are encouraged. Furthermore, authors studying the role of the bone marrow in the induction and maintenance of long-term B cell memory in terms of IgM, IgG and IgA-secreting acute and memory cells are also welcomed.