Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors

Kräutler, Nike Julia; Kana, Veronika; Kranich, Jan; Tian, Yinghua; Perera, Dushan; Lemm, Doreen; Schwarz, Petra; Armulik, Annika; Browning, Jeffrey L.; Tallquist, Michelle D.; Buch, Thorsten; Oliveira-Martins, José B.; Zhu, Chuanbing; Hermann, Mario; Wagner, Ulrich; Brink, Robert; Heikenwälder, Mathias; Aguzzi, Adriano

doi:10.1016/j.cell.2012.05.032

Cited by 358 publications

(347 citation statements)

References 70 publications

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“…Indeed, we could label (i) sinus lining cells, (ii) MRCs, and (iii) FDCs with the same marker (CD83). Curiously, these cells were all infected by BTV, whereas we never observed BTV replication in the stromal cells of the T-cell area (which do not express CD83) or in pericytes surrounding the high endothelial venules, which have been proposed to be the progenitor of FDC in the mouse spleen (38). The origin of LN FDC is still debated; however, the data shown here might indirectly suggest that because these different stromal cell populations are all targeted by BTV (an endotheliotropic virus), they could potentially share the same endothelial origin.…”

Section: Discussionmentioning

confidence: 90%

Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression

Melzi

Caporale

Rocchi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Arboviruses cause acute diseases that increasingly affect global health. We used bluetongue virus (BTV) and its natural sheep host to reveal a previously uncharacterized mechanism used by an arbovirus to manipulate host immunity. Our study shows that BTV, similarly to other antigens delivered through the skin, is transported rapidly via the lymph to the peripheral lymph nodes. Here, BTV infects and disrupts follicular dendritic cells, hindering B-cell division in germinal centers, which results in a delayed production of high affinity and virus neutralizing antibodies. Moreover, the humoral immune response to a second antigen is also hampered in BTV-infected animals. Thus, an arbovirus can evade the host antiviral response by inducing an acute immunosuppression. Although transient, this immunosuppression occurs at the critical early stages of infection when a delayed host humoral immune response likely affects virus systemic dissemination and the clinical outcome of disease.arbovirus | immunosuppression | follicular dendritic cells | bluetongue | lymph node

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Section: Discussionmentioning

confidence: 90%

Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression

Melzi

Caporale

Rocchi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…32 Recently, a PDGFRb þ perivascular cell population has been described to give rise to follicular dendritic cells that may appear de novo in chronically inflamed tissue. 33 We are Quantification of collagen VI þ fibers in the ischemic tissue. While no difference in collagen VI density was observed in the acute lesion, it rose markedly in subacute ischemic lesions.…”

Section: Discussionmentioning

confidence: 99%

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

Fernández-Klett

Potas

Hilpert

et al. 2012

J Cereb Blood Flow Metab

208

249

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Despite its limited regenerative capacity, the central nervous system (CNS) shares more repair mechanisms with peripheral tissues than previously recognized. Scar formation is a ubiquitous healing mechanism aimed at patching tissue defects via the generation of fibrous extracellular matrix (ECM). This process, orchestrated by stromal cells, can unfavorably affect the capacity of tissues to restore function. Vascular mural cells have been found to contribute to scarring after spinal cord injury. In the case of stroke, little is known about the responses of pericytes (PCs) and stromal cells. Here, we show that capillary PCs are rapidly lost after cerebral ischemia in both experimental and human stroke. Coincident with this loss is a massive proliferation of resident platelet-derived growth factor receptor beta (PDGFRb) þ and CD105 þ stromal cells, which originate from the neurovascular unit and deposit ECM in the ischemic mouse brain. The presence of PDGFRb þ stromal cells demarcates a fibrotic, contracted, and macrophage-laden lesion core from the rim of hypertrophic astroglia in both experimental and human stroke. We suggest that a previously unrecognized population of CNS-resident stromal cells drives a dynamic process of scarring after cerebral ischemia, which appears distinct from the glial scar and represents a novel target for regenerative stroke therapies.

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“…FDC secrete chemokines and survival factors important for GC structure and function (8). The maintenance of FDC maturation status (phenotype and function) requires constitutive signaling through the lymphotoxin (LT) b receptor (LTbR); FDC are induced to mature in situ from a perivascular precursor through engagement of LTbR by membrane-bound LTab expressed on lymphocytes (9,10). Within the GC, B cells express even higher levels of LTab, which is likely important for orchestrating a tight FDC network to support maturation of the Ab response (11,12).…”

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confidence: 99%

AID-Expressing Germinal Center B Cells Cluster Normally within Lymph Node Follicles in the Absence of FDC-M1+ CD35+ Follicular Dendritic Cells but Dissipate Prematurely

Boulianne

Ward

et al. 2013

The Journal of Immunology

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Upon activation with T-dependent Ag, B cells enter germinal centers (GC) and upregulate activation-induced deaminase (AID). AID+ GC B cells then undergo class-switch recombination and somatic hypermutation. Follicular dendritic cells (FDC) are stromal cells that underpin GC and require constitutive signaling through the lymphotoxin (LT) β receptor to be maintained in a fully mature, differentiated state. Although it was shown that FDC can be dispensable for the generation of affinity-matured Ab, in the absence of FDC it is unclear where AID expression occurs. In a mouse model that lacks mature FDC, as well as other LT-sensitive cells, we show that clusters of AID+PNA+GL7+ Ag-specific GC B cells form within the B cell follicles of draining lymph nodes, suggesting that FDC are not strictly required for GC formation. However, later in the primary response, FDC-less GC dissipated prematurely, correlating with impaired affinity maturation. We examined whether GC dissipation was due to a lack of FDC or other LTβ receptor–dependent accessory cells and found that, in response to nonreplicating protein Ag, FDC proved to be more critical for long-term GC maintenance. Our study provides a spatial-temporal analysis of Ag-specific B cell activation and AID expression in the context of a peripheral lymph node that lacks FDC-M1+ CD35+ FDC and other LT-sensitive cell types, and reveals that FDC are not strictly required for the induction of AID within an organized GC-like environment.

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Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors

Cited by 358 publications

References 70 publications

Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression

Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

AID-Expressing Germinal Center B Cells Cluster Normally within Lymph Node Follicles in the Absence of FDC-M1+ CD35+ Follicular Dendritic Cells but Dissipate Prematurely

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