Abstract
Immune memory — comprising T cells, B cells and plasma cells and their secreted antibodies — is crucial for human survival. It enables the rapid and effective clearance of a pathogen after re-exposure, to minimize damage to the host. When antigen-experienced, memory T cells become activated, they proliferate and produce effector molecules at faster rates and in greater magnitudes than antigen-inexperienced, naive cells. Similarly, memory B cells become activated and differentiate into antibody-secreting cells more rapidly than naive B cells, and they undergo processes that increase their affinity for antigen. The ability of T cells and B cells to form memory cells after antigen exposure is the rationale behind vaccination. Understanding immune memory not only is crucial for the design of more-efficacious vaccines but also has important implications for immunotherapies in infectious disease and cancer. This ‘guide to’ article provides an overview of the current understanding of the phenotype, function, location, and pathways for the generation, maintenance and protective capacity of memory T cells and memory B cells.
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Glossary
- Antibody isotypes
-
The designation of an immunoglobulin chain in respect to its constant regions. Light chains can be of either κ or λ isotype. Heavy chains can be of μ, δ, γ, α or ε isotype, which determines IgM, IgD, IgG, IgA or IgE antibodies, respectively.
- Antigen-presenting cells
-
(APCs). Immune cells such as dendritic cells, macrophages, Langerhans cells and B cells that process and present antigens on MHC molecules for recognition by the T cell receptor or B cell receptor of T cells or B cells, respectively.
- ATAC-seq
-
Assay for transposase-accessible chromatin with sequencing, which is a method to identify open, accessible chromatin regions using mutated hyperactive transposase.
- ChIP-seq
-
Chromatin immunoprecipitation followed by sequencing, which is a genome-wide method to identify DNA binding sites for transcription factors and other proteins.
- Class-switch recombination
-
(CSR). A somatic gene recombination process in activated B cells that replaces the heavy-chain constant region of an immunoglobulin with one of a different isotype, for example inducing a switch from IgM or IgD to IgG, IgA or IgE.
- Complement
-
A set of plasma proteins that can kill extracellular pathogens directly or coat (opsonize) them so that they can be removed by phagocytes.
- Cytometry by time of flight
-
(CyTOF). An application of mass cytometry to study protein expression at the single-cell level.
- DNA footprinting
-
A method to study whether a protein binds to a specific DNA region of interest.
- Fate-mapping
-
Application of technologies to ‘mark’ cells and track their fate and the fate of their progeny.
- Germinal centres
-
(GCs). Sites of high-level B cell proliferation and differentiation that develop in lymphoid follicles during an adaptive immune response.
- Immunosenescence
-
Immune dysfunction that occurs with ageing, associated with defects in cell function and quantity.
- MHC restriction
-
A property of T cells whereby the T cell receptor recognizes antigen only when bound to an MHC molecule on an antigen-presenting cell as a peptide–MHC complex.
- MHC-tetramer
-
A complex of four antigen-specific, peptide-bound MHC molecules attached to a streptavidin-coated bead.
- Neutralization
-
Inhibition of the infectivity of a virus or the toxicity of a toxin molecule by the direct binding of antibodies.
- Opsonization
-
The coating of the surface of a pathogen by antibody and/or complement that makes it more readily ingested by phagocytes.
- Retrospective 14C birth dating
-
A process through which levels of 14C in cellular DNA are measured and their chronological age calculated based on known levels of atmospheric 14C, which increased in the 1960s and 1970s because of nuclear weapons testing and declined thereafter.
- Somatic hypermutation
-
(SHM). A mechanism by which mutations are induced in the variable-region DNA of rearranged immunoglobulin genes to produce variant immunoglobulins, some of which bind antigen with a greater affinity.
- T follicular helper cells
-
(TFH cells). A CD4+ T cell subset found in lymphoid follicles that promotes B cell differentiation through interaction of the co-stimulatory molecule CD40L with CD40 on B cells and by producing the cytokine IL-21.
- Time-stamping
-
A technology of in situ lineage tracing using the tamoxifen-inducible Cre-recombinase system.
- Unfolded protein response
-
A cellular stress response that is activated when unfolded proteins accumulate in the endoplasmic reticulum in the cell.
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Lam, N., Lee, Y. & Farber, D.L. A guide to adaptive immune memory. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-024-01040-6
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DOI: https://doi.org/10.1038/s41577-024-01040-6
