Immunological memories of the bone marrow

Abstract

SummaryMemory 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.

Mobilization of tissue-resident memory CD4+ T lymphocytes and their contribution to a systemic secondary immune reaction

“…Antigen-specific memory provided by the adaptive immune system is multi-layered. Antibodies secreted by memory plasma cells provide immediate protection, while memory T and B lymphocytes provide reactive memory against excessive or modified antigen [9,30]. Moreover, immune memory cells are compartmentalized in various tissues [9,31].…”

“…Antibodies secreted by memory plasma cells provide immediate protection, while memory T and B lymphocytes provide reactive memory against excessive or modified antigen [9,30]. Moreover, immune memory cells are compartmentalized in various tissues [9,31]. We have previously shown that prominent populations of memory plasma cells and memory CD4 + and CD8 + T lymphocytes reside and rest in the bone marrow [7,8,11,16].…”

“…Tissue-resident memory T cells have been decribed for a variety of tissues, such as the skin, gut, lungs, liver [2][3][4][5][6], and bone marrow [7][8][9][10][11]. Compartments of tissue-resident memory T cells have been defined by confinement in parabiosis experiments [12,13], by distinct gene expression signatures [4,7,11,[14][15][16], and by exclusive antigen receptor repertoires and specificities [3,7,11].…”

Stromal cell-contact dependent PI3K and APRIL induced NF-κB signaling complement each other to prevent mitochondrial- and endoplasmic reticulum stress induced cell death of bone marrow plasma cells

“…Long-lived memory plasma cells persist for a lifetime in mice (Manz, Thiel, & Radbruch, 1997;Slifka, Antia, Whitmire, & Ahmed, 1998), non-human primates (Hammarlund et al, 2017) and in humans (Landsverk et al, 2017). They form an independent population of memory cells (Chang, Tokoyoda, & Radbruch, 2018;Radbruch et al, 2006). Memory plasma cells are evenly distributed throughout the bone marrow and most if not all of them directly contact a mesenchymal stromal cell (Zehentmeier et al, 2014).…”

Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow

“…While the generation of memory B lymphocytes and their role in secondary immune responses has been subject of intense research, little is known about their maintenance over time in the apparent absence of antigen. For memory T lymphocytes, relatively new research has unveiled a highly structured organization of their maintenance, describing populations of 225 circulating and tissue-resident memory T cells (Trm)2 . Trm have been described for nearly all organs investigated, including the BM6, 7,29 .…”