Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches

Sapoznikov, Anita; Pewzner-Jung, Yael; Kalchenko, Vyacheslav; Krauthgamer, Rita; Shachar, Idit; Jung, Steffen

doi:10.1038/ni1571

Cited by 169 publications

(186 citation statements)

References 55 publications

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“…With our system, we did not observe enrichment of IL-15-expressing cells in proximity to the CD8 + memory T cells, as we found less than 2% of memory T cells in contact with IL-15 + cells. This might be due to the limited sensitivity of the IL-15 antibody stain, resulting in us only detecting cells with the highest IL-15 expression.It has been reported that adoptively transferred leukemic cells as well as DCs and B cells populate perivascular regions in cranial bones of mice [44,45]. In contrast to those studies, we did not observe enrichment of the transferred memory T cells to subregions within the BM, rather they were found randomly scattered throughout the BM.…”

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confidence: 99%

Contribution of 4–1BBL on radioresistant cells in providing survival signals through 4–1BB expressed on CD8+ memory T cells in the bone marrow

et al. 2012

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The persistence of memory lymphocytes is a critical feature of adaptive immunity. The TNF family ligand 4-1BBL supports the antigen-independent survival of CD8 + memory T cells. Here, we show that mice lacking 4-1BB only on αβ T cells show a similar defect in CD8 + T-cell recall responses, as previously shown in 4-1BBL-deficient mice. We show that 4-1BB is selectively expressed on BM CD8 + but not CD4 + memory T cells of unimmunized mice. Its ligand, 4-1BBL, is found on VCAM-1 + stromal cells, CD11c + cells, and a Gr1 lo myeloid population in unimmunized mice. Adoptive transfer of in vitro generated memory T cells into mice lacking 4-1BBL only on radioresistant cells recapitulates the defect in CD8 + T-cell survival seen in the complete knockout mice, with smaller effects of 4-1BBL on hematopoietic cells. In BM, adoptively transferred DsRed CD8 + memory T cells are most often found in proximity to VCAM-1 + cells or Gr1 + cells, followed by B220 + cells and to a much lesser extent near CD11c + cells. Thus, a VCAM-1 + CD45 − stromal cell is a plausible candidate for the radioresistant cell that provides 4-1BBL to CD8 + memory T cells in the BM.Keywords: 4-1BB r Bone marrow chimeras r CD8 + T-cell memory r CD137 r Stromal cells Supporting Information available online IntroductionImmunological memory is a key feature of our adaptive immune system. The persistence of memory lymphocytes affords the host long-term protection against reinfection. It is thought that lymphocytes must compete for space in defined cellular niches that are specific to a particular subset of lymphocytes [1,2]. The cell types and key molecular components that make up the supportCorrespondence: Dr. Tania H. Watts e-mail: tania.watts@utoronto.ca ive niches for memory T cells are beginning to be defined [3][4][5][6]. These niches are expected to contain the chemokines that attract the lymphocytes to the site [3,7], the adhesion molecules that provide retention signals at the site [5,7], as well as the common γ-chain (γ c ) cytokines that provide homeostatic proliferative signals to the lymphocytes [8].For CD8 + T cells, there is strong evidence that both IL-15 and IL-7 are required for their maintenance [8][9][10][11][12][13][14][15][16][17]. CD8 + CD44 Hi memory phenotype T cells home to and are enriched in the BM [7,18]. Moreover, the BM contains virus-specific memory T cells that can protect against reinfection [19], and CD8 + memory T cells in the BM show evidence of homeostatic proliferation C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 2862 Gloria H. Y. Lin et al. Eur. J. Immunol. 2012. 42: 2861-2874 [20,21], independently of secondary lymphoid organs [22]. Thus, it has been proposed that the BM is a major site for homeostatic proliferation of CD8 + memory T cells [23]. However, there is limited evidence as to the nature of the BM niches that support the proliferation and survival of these cells. In addition to a requirement for chemokines, γ c cytokines, and adhesion molecules, emerging data also suggest that ligan...

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confidence: 99%

Contribution of 4–1BBL on radioresistant cells in providing survival signals through 4–1BB expressed on CD8+ memory T cells in the bone marrow

et al. 2012

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“…The amplified memory T lymphocytes relocate to memory niches and return to proliferative and functional rest. Such immune clusters131, 152 or immune niches153 had been observed before, but their context had remained obscure. It seems that they serve mainly to amplify the antigen‐specific memory T lymphocytes.…”

Section: Reactivation Of Bone Marrow Memory T Lymphocytesmentioning

confidence: 90%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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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.

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“…Recent models in which pDCs are selectively eliminated highlight their contributions in some, but not all, settings of infections by pathogens [18;19]. The cDC subsets appear to be primarily concerned with priming adaptive immune responses, particularly those of T cells, although important interactions with other immune cells, such as B cells and NK cells, have also been described [20][21][22].…”

Section: Unique Functions and Subsets Of DC Lineagesmentioning

confidence: 99%

Transcription factor networks in dendritic cell development

Satpathy

Murphy

2011

Seminars in Immunology

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Dendritic cells (DCs) are a heterogeneous population within the mononuclear phagocyte system (MPS) that derive from bone marrow precursors. Commitment and specification of hematopoietic progenitors to the DC lineage is critical for the proper induction of both immunity and tolerance. This review summarizes the important cytokines and transcription factors required for differentiation of the DC lineage as well as further diversification into specific DC subsets. We highlight recent advances in the characterization of immediate DC precursors arising from the common myeloid progenitor (CMP). Particular emphasis is placed on the corresponding temporal expression of relevant factors involved in regulating developmental options.

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Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches

Cited by 169 publications

References 55 publications

Contribution of 4–1BBL on radioresistant cells in providing survival signals through 4–1BB expressed on CD8+ memory T cells in the bone marrow

Contribution of 4–1BBL on radioresistant cells in providing survival signals through 4–1BB expressed on CD8+ memory T cells in the bone marrow

Immunological memories of the bone marrow

Transcription factor networks in dendritic cell development

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