In vivo imaging of germinal centres reveals a dynamic open structure

Schwickert, Tanja A.; Lindquist, Randall L.; Shakhar, Guy; Livshits, Geulah; Skokos, Dimitris; Kosco‐Vilbois, Marie H.; Dustin, Michael L.; Nussenzweig, Michel C.

doi:10.1038/nature05573

Cited by 422 publications

(480 citation statements)

References 27 publications

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“…The germinal centers of secondary lymphoid follicles are recognized as dynamic structures where B cells undergo clonal expansion, class switching, antibody gene diversification, and affinity maturation (Schwickert et al, 2007). The presence of a large number of germinal centers was a common finding and suggests proficient B-cell function (i.e., antibody response) in the devils.…”

Section: Lymphoid Tissues Of the Tasmanian Devilmentioning

confidence: 99%

A Histological and Immunohistochemical Analysis of Lymphoid Tissues of the Tasmanian Devil

Kreiss

Obendorf

Hemsley

et al. 2009

The Anatomical Record

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Tasmanian devil lymphoid tissues (thymus, spleen, and lymph node) from seven animals, including pouch young, juvenile, and adult devils, were investigated using histological and immunohistochemical techniques. Antibodies against the conserved intracytoplasmic portion of CD3 and CD79b (T-and B-cell markers, respectively) and MHC II were used to label immune cells. The thymus from the juvenile devils and the pouch young had CD3þ cells that were primarily located in the medulla of the organ. The spleen consisted of red and white pulp areas with characteristic lymphoid follicles with CD79bþ and MHC IIþ cells and nonfollicular T-cell-dominated periarteriolar lymphoid sheaths. Peripheral lymph nodes presented three distinct regions, outer cortex and medulla (both with primarily CD79bþ and MHC IIþ cells) and paracortex (mainly CD3þ cells). Tissue architecture and distribution of the immune cells were similar to that seen in eutherian mammals and other marsupials, indicating that the Tasmanian devil has all the structural elements necessary for effective adaptive immunity. Anat Rec, 292:611-620, 2009. V V C 2009 Wiley-Liss, Inc.

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Section: Lymphoid Tissues Of the Tasmanian Devilmentioning

confidence: 99%

A Histological and Immunohistochemical Analysis of Lymphoid Tissues of the Tasmanian Devil

Kreiss

Obendorf

Hemsley

et al. 2009

The Anatomical Record

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“…By the use of two-photon laser-scanning microscopy e.g. Schwickert et al could show in mice that germinal centres reveal a dynamic open structure (19). In a recently published paper, Boissonnas et al could show in vivo imaging of cytotoxic T cell infiltration and the elimination of a solid tumor by the use of twophoton intravital microscopy (20).…”

Section: Two Photon Fluorescence Microscopymentioning

confidence: 99%

In vivo imaging in experimental preclinical tumor research–A review

et al. 2007

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The multiparametric molecular cell and tissue analysis in vitro and in vivo is characterized by rapid progress in the field of image generation technologies, sensor biotechnology, and computational modeling. Fascinating new potentials in unraveling the detailed functions of single cells, organs, and whole organisms are presently emerging and permit the close monitoring i.e. tumor development or basic cell development processes with an unprecedented multiplicity of promising investigative possibilities. To answer basic questions of in vivo tumor development and progression fluorescence based imaging techniques provide new insights into molecular pathways and targets. Genetic reporter systems (eGFP, DsRED) are available and high sensitive detection systems are on hand. These techniques could be used for in vitro assays and quantified e.g. by microscopy and CCD based readouts. The introduction of novel fluorescent dyes emitting in the near infrared range (NIR) combined with the development of sensitive detector systems and monochromatic powerful NIR-lasers for the first time permits the quantification and imaging of fluorescence and/or bioluminescence in deeper tissues. Laser based techniques particularly in the NIR-range (like two-photon microscopy) offer superb signal to noise ratios, and thus the potential to detect molecular targets in vivo. In combination with flat panel volumetric computed tomography (fpVCT), questions dealing e.g. with tumor size, tumor growth, and angiogenesis/vascularization could be answered noninvasively using the same animal. The resolution of down to 150 lm/each direction can be achieved using fpVCT. It is demonstrated by many groups that submillimeter resolutions can be achieved in small animal imaging at high sensitivity and molecular specificity. Since the resolution in preclinical small animal imaging is down to $10 lm by the use of microCT and to subcellular resolutions using ($1 lm) microscope based systems, the advances of different techniques can now be combined to ''multimodal'' preclinical imaging and the possibilities for in vivo intravital cytometry now become within one's reach. ' International Society for Analytical CytologyKey terms molecular imaging; optical imaging; tumor imaging; fpVCT; near infrared range imaging; renal cell carcinoma; in vivo cytometry; fluorescence in vivo imaging MOLECULAR AND OPTICAL IMAGING--DEFINITIONSMolecular Imaging is a rapidly expanding field in which the modern tools of molecular cell biology are being married to state of the art technology for noninvasive imaging.Within the last years, crucial improvements, notably in optical resolution, have been made. This is a very promising field which actually aims at developing different tools, reagents, and methods to image specific molecular pathways in humans and animals, e.g. those that are key targets in tumor development.Many of these novel imaging techniques could be used for preclinical small animal imaging, for example tumor research, today. Next to fascinating high resolution, t...

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“…Shortly after this, the Wrst papers investigating cell migration in explanted lymph nodes or thymic stromal reaggregate cultures (Bousso et al 2002) were published, followed by true intravital studies (Gunzer et al 2004;Mempel et al 2004). Meanwhile the number of reports using intravital 2PM for immunological questions has risen enormously, spanning from the cellular events of T cell activation (Miller et al 2004a), formation and function of germinal centers (Allen et al 2007b;Schwickert et al 2007) or function of regulatory T cells (Tadokoro et al 2006) to complex processes such as granuloma formation ) and the delivery of antigens (Carrasco and Batista. 2007;Qi et al 2006) or viruses to B cells (Junt et al 2007a).…”

Section: Analysis Of Cell Migration In Vivomentioning

confidence: 99%

“…Thus, XFP-based approaches to label the FDC network rely on complicated strategies of radiation chimaeras exploiting the ability of FDC to resist radiation-mediated ablation (BajenoV et al 2006;Victoratos et al 2006). In contrast, a very simple, yet functional approach to stain FDC is the injection of FDC-speciWc Xuorescent antibodies subcutaneously (Schwickert et al 2007) (Fig. 1e).…”

Section: Visualization Of Leukocytes and Organ Structurementioning

confidence: 99%

“…For a long time, it was a matter of debate whether there was the possibility for centrocytes to become centroblasts again and go back from the light-to the dark zone in a process called recirculation or recycling (Meyer-Hermann and Maini 2005). It was only possible to address by direct imaging of the GC reaction, what is actually happening and, consequently, one of the prime targets of the Wrst set of three imaging studies on the germinal center response was the analysis of just this parameter (Allen et al 2007b;Hauser et al 2007;Schwickert et al 2007). However, this example also demonstrates the diYculties in coming to generally accepted conclusions.…”

Section: Impact Of Imaging Studies On Cell Migration For Understandinmentioning

confidence: 99%

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3D and 4D imaging of immune cells in vitro and in vivo

Nitschke

Garin

Kosco‐Vilbois

et al. 2008

Histochem Cell Biol

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Analyzing the dynamics of cellular immune responses, although performed for decades in immunologic research, has seen an enormous increase in the number of studies using this approach since the development of intravital 2-photon microscopy. Meanwhile, new insights into the dynamics of cellular immunity are being published on a daily basis. This review gives a short overview of the currently most widely used techniques, both on the microscopy side as well as on the experimental part. DiYculties and promises will be discussed. Finally, a personal selection of the most interesting Wndings of the Wrst 6 years of intravital 2-photon microscopy for immunological questions will be given. The overall aim is to get the reader interested into this fascinating way of investigating the immune response by means of "dynamic histology". This already has and will continue to broaden our view on how immune cells work in real life.

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In vivo imaging of germinal centres reveals a dynamic open structure

Cited by 422 publications

References 27 publications

A Histological and Immunohistochemical Analysis of Lymphoid Tissues of the Tasmanian Devil

A Histological and Immunohistochemical Analysis of Lymphoid Tissues of the Tasmanian Devil

In vivo imaging in experimental preclinical tumor research–A review

3D and 4D imaging of immune cells in vitro and in vivo

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