Immunological memories of the bone marrow

Memory for antigens once encountered is a hallmark of the immune system of vertebrates, providing us with an immunity adapted to pathogens of our environment. Despite its fundamental relevance, the cells and genes representing immunological memory are still poorly understood. Here we discuss the concept of a circulating, proliferating, and ubiquitous population of effector lymphocytes vs concepts of resting and dormant populations of dedicated memory lymphocytes, distinct from effector lymphocytes and residing in defined tissues, particularly in barrier tissues and in the bone marrow. The lifestyle of memory plasma cells of the bone marrow may serve as a paradigm, showing that persistence of memory lymphocytes is not defined by intrinsic “half‐lives”, but rather conditional on distinct survival signals provided by dedicated niches. These niches are organized by individual mesenchymal stromal cells. They define the capacity of immunological memory and regulate its homeostasis.

• Publication year

  2018

• Venue

  Immunological Reviews

• Publication date

  2018-04-17

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/imr.12656PMID 29664564PMCID 5947123
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2016cited by this paper
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  2015cited by this paper
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  2015cited by this paper
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  2015cited by this paper
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  2014cited by this paper
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  2014cited by this paper
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  2014cited by this paper
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  2014cited by this paper
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  2014cited by this paper
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  2014cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2008cited by this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper