Alternative cell types form a Multi-Component-Plasma-Cell-Niche

Winter, Oliver; Mohr, Elodie; Manz, Rudolf A.

doi:10.1016/j.imlet.2011.07.006

Cited by 11 publications

(13 citation statements)

References 10 publications

(6 reference statements)

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“…Longitudinal studies of the frequency of antigenspecific plasma cells have demonstrated that a finite number of 'niches' exist in the bone marrow 8 . The cellular nature of these niches has been the subject of numerous studies and remains contentious, with several distinct cellular lineages proposed as niche components (recently reviewed in REFS 132,142,143). While it is outside the scope of this Review to discuss the many competing models of the plasma cell niche, it seems likely in the bone marrow to consist of at least a CXCL12 + VCAM1 + stromal cell 144 cell that secretes the B cell survival factor a proliferationinducing ligand (APRIL; also known as TNFSF13) (FIG.…”

Section: Plasma Cell Homing and Survivalmentioning

confidence: 99%

The generation of antibody-secreting plasma cells

et al. 2015

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The regulation of antibody production is linked to the generation and maintenance of plasmablasts and plasma cells from their B cell precursors. Plasmablasts are the rapidly produced and short-lived effector cells of the early antibody response, whereas plasma cells are the long-lived mediators of lasting humoral immunity. An extraordinary number of control mechanisms, at both the cellular and molecular levels, underlie the regulation of this essential arm of the immune response. Despite this complexity, the terminal differentiation of B cells can be described as a simple probabilistic process that is governed by a central gene-regulatory network and modified by environmental stimuli.

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Section: Plasma Cell Homing and Survivalmentioning

confidence: 99%

The generation of antibody-secreting plasma cells

et al. 2015

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“…In secondary lymphatic tissues, PCs reside in extrafollicular areas such as the lamina propria of mucosa and the red pulp of spleen, and LLPCs are associated with APRIL, BAFF, and IL-6 sources in the vicinity (14,15,22,23). Whereas APRIL is produced by several cell types in the bone marrow (24), only few cells in specific areas (e.g., the subepithelium zone in tonsillar crypts or intestinal villi in the mucosa) secrete this survival factor in other organs (15). Moreover, certain organs have different potential to support PC survival, and induction of angiogenesis seems crucial to maintain PCs in inflamed tissues (25).…”

mentioning

confidence: 99%

“…As such, some cell types may specifically support LLPCs in the bone marrow sustaining stable/long-term humoral memory, whereas others provide PC survival in secondary lymphoid organs or inflamed tissues during chronic inflammation or infection, maintaining temporary/short-term humoral memory. Considering recent findings, we extended the classical stroma/ plasma cell model of the survival niche with a hematopoietic niche component (HNC) to the model of a multicomponent PC niche (MCPN) (24) (Fig. 1A).…”

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confidence: 99%

Pathogenic Long-Lived Plasma Cells and Their Survival Niches in Autoimmunity, Malignancy, and Allergy

Winter

Dame

Jundt

et al. 2012

The Journal of Immunology

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Long-lived plasma cells survive in a protected microenvironment for years or even a lifetime and provide humoral memory by establishing persistent Ab titers. Long-lived autoreactive, malignant, and allergen-specific plasma cells are likewise protected in their survival niche and are refractory to immunosuppression, B cell depletion, and irradiation. Their elimination remains an essential therapeutic challenge. Recent data indicate that long-lived plasma cells reside in a multicomponent plasma cell niche with a stable mesenchymal and a dynamic hematopoietic component, both providing essential soluble and membrane-bound survival factors. Alternative niches with different hematopoietic cell components compensate fluctuations of single cell types but may also harbor distinct plasma cell subsets. In this Brief Review, we discuss conventional therapies in autoimmunity and multiple myeloma in comparison with novel drugs that target plasma cells and their niches. In the future, such strategies may enable the specific depletion of pathogenic plasma cells while leaving the protective humoral memory intact.

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“…T cell-dependent primary immunization was performed at the age of 9.5 wk and secondary immunizations at the age of 11.5 and 13.5 wk (results are presented in Figs. [5][6][7][8].…”

Section: Methodsmentioning

confidence: 99%

“…Bone is also the preferential homing site for subclasses of mature B and T cells such as CD8-positive and CD4-positive memory T cells and regulatory T cells (3,4) as well as long-lived plasma cells (5)(6)(7)(8).…”

mentioning

confidence: 99%

Inhibition of Bone Remodeling in Young Mice by Bisphosphonate Displaces the Plasma Cell Niche into the Spleen

Teufel

Grötsch

Luther

et al. 2014

The Journal of Immunology

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The bone marrow provides niches for early B cell differentiation and long-lived plasma cells. Therefore, it has been hypothesized that perturbing bone homeostasis might impact B cell function and Ab production. This hypothesis is highly relevant for patients receiving long-term treatment with antiresorptive drugs. We therefore analyzed the humoral immune response of mice chronically treated with ibandronate, a commonly used bisphosphonate. We confirmed the increased bone mass caused by inhibition of osteoclast activity and also the strongly reduced bone formation because of decreased osteoblast numbers in response to ibandronate. Thus, bisphosphonate drastically inhibited bone remodeling. When ibandronate was injected into mice after a primary immunization to mimic common antiosteoporotic treatments, the generation of the various B cell populations, the response to booster immunization, and the generation of plasma cells were surprisingly normal. Mice also responded normally to immunization when ibandronate was applied to naive mice. However, there, ibandronate shunted the homing of bone marrow plasma cells. Interestingly, ibandronate reduced the numbers of megakaryocytes, a known component of the bone marrow plasma cell niche. In line with normal Ab responses, increased plasma cell populations associated with increased megakaryocyte numbers were then observed in the spleens of the ibandronate-treated mice. Thus, although inhibition of bone remodeling disturbed the bone marrow plasma cell niche, a compensatory niche may have been created by relocating the megakaryocytes into the spleen, thereby allowing normal B cell responses. Therefore, megakaryocytes may act as a key regulator of plasma cell niche plasticity.

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Alternative cell types form a Multi-Component-Plasma-Cell-Niche

Cited by 11 publications

References 10 publications

The generation of antibody-secreting plasma cells

The generation of antibody-secreting plasma cells

Pathogenic Long-Lived Plasma Cells and Their Survival Niches in Autoimmunity, Malignancy, and Allergy

Inhibition of Bone Remodeling in Young Mice by Bisphosphonate Displaces the Plasma Cell Niche into the Spleen

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